43:1 February 2016 43:1 February iseases Mycotoxins, food security and climate change food Mycotoxins, A plague on our ashes fungus Candida – living with a killer faces of cryptococci peaches to patients: the many From The hidden viruses of the fungal kingdom Fungal D Microbiology TODAY

Microbiology Today 43:1 February 2016 Fungal Diseases

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Journal: Journal: Microbiology Today Microbiology Essential Generics: Chloramphenical Ad Chloramphenical Generics: Essential 04/12/2015 11:51 CHL25060 O65995 ALLIANCE: MOVIANTO: AAH: CHL600B PIP: 106-5796 CAPSULES

CHLORAMPHENICOL 1 2 3,4 Adverse events should be reported. Reporting forms be reported. Adverse events should can be found at www.mhra.gov.uk/ and information events should also be reported to yellowcard. Adverse Essential Generics on 01784 477167. irregular respiration and death within a few hours of the onset of irregular respiration and death within a few hours of the onset symptoms. Overdose: Stop chloramphenicol immediately if signs of adverse events oral develop. Treatment is mainly supportive. If an allergy develops, Baby antihistamines may be used. In severe overdosage e.g. Gray Resin Syndrome, reduce plasma levels of chloramphenicol rapidly. increase haemoperfusion (XAD-4) has been reported to substantially chloramphenicol clearance. Pack size and Price: 60 capsules £377.00 Legal Category: POM. Market Authorisation Number: PL17736/0075. Market Authorisation Holder: Chemidex Pharma Limited, 7 Egham UK. Business Village, Crabtree Road, Egham, Surrey TW20 8RB, Date of preparation: October 2014. for See Chloramphenicol Capsules Summary of Product Characteristics full prescribing information. References: 1. Martindale: The Complete Drug Reference. Chloramphenicol. [Online]. Available from: http://www.medicinescomplete.com [Accessed 17th September 2015]. 2. Fluit, A.C., Wielders, C.L.C., Verhoef, J., and Schmitz, F.J. Epidemiology and susceptibility of 3,051 Staphylococcus aureus isolates from 25 university hospitals participating in the European SENTRY Study. Journal of Clinical Microbiology. 2001; 39(10): 3727-3732. 3. Kelly, C., LaMont, T. Patient information: Antibiotic- cile). www.uptodate.com. 2011. associated diarrhea (Clostridium diffi 4. Bartlett J.G. et al. Antimicrobial agents implicated in Clostridium cile toxin-associated diarrhea of colitis. Johns Hopkins Med J. 1981; diffi 149(1): 6-9. 5. Feder. H, Chloramphenicol: What we have learned in the last decade. Southern Medical Journal. 1986; (79)9: 1129-34. 6. Weigel LM et al. High-level vancomycin-resistant Staphylococcus aureus (VRSA) lm. Antimicrobial Agents and associated with a polymicrobial biofi Chemotherapy. Published online ahead of print on 30th October 2006. http://aac.asm.org/cgi/reprint/AAC.00576-06v1.pdf. (Accessed on 17th September 2015). 7. Ensminger, P., Counter, F., Thomas, L., Lebbehuse, P. Susceptibility, resistance development, and synergy of antimicrobial cile. Current Microbiology. combinations against Clostridium diffi 1982; 7: 59-62. 8. Poilane, I., Bert, F., Cruaud, P., Nicolas-Chanoine, MH., Collignon, A. Interest of the disk diffusion method for screening cile isolates with decreased susceptibility to antibiotics. Clostridium diffi Pathologie Biologie (Paris). 2007; 55(8-9): 429-33. 9. Cattoir, V., Ould-Hocine, ZF., Legrand, P. Antimicrobial susceptibility of Clostridium cile clinical isolates collected from 2001 to 2007 in a French diffi university hospital. Pathologie Biologie (Paris). 2008; 56(7-8): 407-11. 10. Brazier, JS., Levett, PN., Stannard, AJ., Phillips, KD., Willis, AT. Antibiotic susceptibility of clinical isolates of clostridia. Journal of Antimicrobial Chemotherapy. 1985; 15(2): 181-5. 1,5 1,5 1,5 7-10 1,5 1,5 1 2 6

Effective against serious Effective against infections including: C.diffi cile with C.diffi implicated Rarely Widely distributed throughout the body, including CSF including the body, throughout distributed Widely levels to i.v. comparable Oral levels C.diffi cile C.diffi E. coli Legionella Rickettsia MRSA VRSA Neisseria H. infl uenzae H. infl Typhoid

For further information, please contact: Essential Generics, 7 Egham Business Village, Crabtree Road, Egham, Surrey TW20 8RB, UK For further information, please contact: Essential Generics, 7 Egham Business Village, Crabtree Road, Abbreviated Prescribing Information Chloramphenicol Capsules BP 250mg Presentation: Hard Gelatin Capsules. particularly Indications: Typhoid fever and life-threatening infections, uenzae, where other antibiotics will those caused by Haemophilus Infl ce. not suffi Posology: For oral administration. doses. For Adults and elderly: 50 mg/kg body weight daily in 4 divided be doubled severe infections (meningitis, septicaemia), this dose may Children: initially, but must be reduced as soon as clinically possible. Not recommended. Contra-indications: Known hypersensitivity or toxic reaction to used chloramphenicol or to any of the excipients. Should not be active for the prophylaxis or treatment of minor infections; during liable to immunisation; in porphyria patients; in patients taking drugs by breast- depress bone marrow function; during pregnancy, labour or feeding mothers. Special warnings and precautions for use: Use only if other treatments are ineffective. Use should be carefully monitored. Reduce dose and monitor plasma levels in hepatic or renal impairment; in the elderly; and in patients concurrently treated with interacting drugs. Interactions: Chloramphenicol prolongs the elimination, increasing the blood levels of drugs including warfarin, phenytoin, sulphonylureas, tolbutamide. Doses of anticonvulsants and anticoagulants may need to be adjusted if given concurrently. Complex effects (increased/ decreased plasma levels) requiring monitoring of chloramphenicol plasma levels have been reported with co-administration of penicillins and rifampicin. Paracetamol prolongs chloramphenicol half-life. Chloramphenicol may increase the plasma levels of calcineurin inhibitors e.g. ciclosporin and tacrolimus. Barbiturates such as phenobarbitone increase the metabolism of chloramphenicol, resulting in reduced plasma chloramphenicol concentrations. In addition, there may be a decrease in the metabolism of phenobarbitone with concomitant chloramphenicol use. There is a small risk that chloramphenicol may reduce the contraceptive effect of oestrogens. Chloramphenicol reduces the response to hydroxocobalamin. Chloramphenicol is contra-indicated in patients taking drugs liable to suppress bone marrow function e.g. carbamazepine, sulphonamides, phenylbutazone, penicillamine, cytotoxic agents, some antipsychotics including clozapine and particularly depot antipsychotics, procainamide, nucleoside reverse transcriptase inhibitors, propylthiouracil. Pregnancy and Lactation: The use of chloramphenicol is contra- indicated as the drug crosses the placenta and is excreted in breast milk. cant effect Effects on ability to drive and use machines: No signifi on driving ability. Undesirable Effects: Reversible dose related bone marrow depression, irreversible aplastic anaemia, increased bleeding time, hypersensitivity reactions including allergic skin reactions, optic neuritis leading to blindness, ototoxicity, acidotic cardiovascular collapse, nausea, vomiting, glossitis, stomatitis, diarrhoea, enterocolitis, Gray Baby Syndrome particularly in the newborn, which consists of abdominal distension, pallid cyanosis, vomiting, progressing to vasomotor collapse, EG/CH/DEC/2015/10 00536_Chloramphenicol Ad_Microbiology Today_AW.indd 1 Editorial

Fungi are widespread in nature and perhaps it is unsurprising that they are often viewed as the benign eukaryotic members of the microbe world. They are responsible for some of the staples of modern living as well as artisan foods, such as leavened bread, blue cheese, craft beer and vintage wines. However, fungi are also responsible for diseases that threaten our food crops and lead to significant economic losses.

aresh Magan and Angel Medina antibiotic was produced by a famous account for almost one million infections explain how fungi produce fungus, Penicillium notatum. However, there per year and around 650,000 deaths. Nmycotoxins that include some of is a dark side to fungi when it comes to Finally, Paul Rowley’s article turns the most toxic naturally-produced human health. The Centers for Disease the tables on fungal infections, examining compounds found in food. The authors Control and Prevention states that “fungal how there are mycoviruses that infect outline how recent predictions suggest infections that are resistant to treatment many important fungi, but often do not that pests and fungal pathogens are are an emerging public health problem”. cause obvious disease within their host. moving at the rate of 5–6 km per year from Although fungal infections contribute Instead it appears that many mycoviruses the equator to the poles with the Earth’s significantly to human morbidity and are beneficial to fungi. This may explain changing climate. These new conditions mortality, their impact on our health is not the widespread distribution of mycoviruses increase the risks of contamination in widely recognised. We have addressed throughout all fungal taxonomic groups. certain regions that are considered to be this concern in this issue. Firstly, Neil Gow, Sowmiya Moorthie and Leila Luheshi ‘bread baskets’ for food production, which Ingrida Raziunaite, Fiona Rudkin, Katja from the PHG Foundation, an independent may lead to increased contamination levels Schaefer and Bhawna Yadav have written thinktank with a special focus on genomics by existing mycotoxins, or emigration of an article that highlights how Candida and other emerging health technologies, other mycotoxins to new regions. thrive as harmless commensal organisms provide this edition’s Comment. They It is not just our food crops that are in our oral cavities, gastrointestinal or discuss how low-cost whole genome being impacted by fungi but some of our urogenital tracts and more rarely on the sequencing technology is beginning to best-loved woodland trees. Anne Edwards skin. Around 50% of us are colonised at any transform the way clinical and public and Allan Downie describe how it became one time without any noticeable symptoms, health microbiologists and epidemiologists evident that ash dieback disease had but these organisms are opportunistic manage the threat of infectious diseases. established in native woodlands in the pathogens that cause infections when our As advances in technology impact east of the UK. They highlight how an immune system is compromised, or our upon our health and our climate, it is clear open access and crowdsourcing approach protective bacterial microflora is depleted. that fungi will continue to demand our led to the establishment of a website Candida is not the only fungus respect as they pose significant threats to (http://oadb.tsl.ac.uk/) used to record causing recent global concern. Since both our environment and our wellbeing. new observations about the disease’s the 1980s, cryptococcal infections have However, as this edition highlights, effective spread. It also provided access to scientific emerged as another major threat to investment in research and developments data, generated by scientists who were human health as a result of the HIV/AIDS in technology may also provide at least establishing a foundation of knowledge pandemic and a more widespread use some of the answers and solutions to this (using genome analysis) about this of immunosuppressive therapies. Paula growing problem. pathogen and the tolerance (resistance) Seoane, Rafael Schneider and Robin C. May map of our native ash trees to this disease. describe how Cryptococcus neoformans Laura Bowater Fungi are also responsible for and Cryptococcus gattii spores are inhaled, Editor revolutionising modern medicine and leading to problems ranging from skin [email protected] health; the first clinically important irritation to blindness; these infections

Microbiology Today Feb 16 | www.microbiologysociety.org 1 Contents

Microbiology TODAY Articles Mycotoxins, food security and climate 10 change: do we know enough? Naresh Magan and Angel Medina The importance of moulds and mycotoxins.

A plague on our ashes 14 Anne Edwards and J. Allan Downie Ash dieback – a new pathogen in Europe that is now in the UK.

Candida – living with a killer fungus 18 Neil A. R. Gow, Ingrida Raziunaite, Fiona M. Rudkin, Katja Schaefer & Bhawna Yadav The global burden of candidiasis.

From peaches to patients: the many 22 faces of cryptococci Paula I. Seoane, Rafael Schneider and Robin C. May Virulent and adaptable Cryptococcus.

The hidden viruses of the fungal 26 kingdom Paul A. Rowley The untapped diversity of mycoviruses. 43:1 February 2016 Features Regulars 34 JMM Case Reports annual round-up 1 Editorial How the journal has developed in 2015. 4 Council 2016 34 Colin Ratledge Center for Microbial Lipids 5 From the President A new research centre for lipid research. 6 From the Chief Executive 35 Grants – Where could a 7 News Microbiology Society grant take you? 30 Annual Conference Read how our grants have helped Dr Lee Sherry. 32 Focused Meetings 36 Schoolzone – Fungi in schools: 46 Reviews a neglected potential Editor Dr Laura Bowater MiSAC and ways to engage pupils with the world of fungi. Managing Editor Ruth Paget 38 Outreach – Editorial Board Phil Aldridge, David Bhella, Helen Brown, Emma Denham, Lorena Fernández-Martínez, Paul Hoskisson, James Redfern, Alison Sinclair, Microbiology comes to Harvey Nichols! Nicola Stonehouse A food microbiology event at Manchester Science Festival. Address Microbiology Society, Charles Darwin House, 12 Roger Street, London WC1N 2JU T +44 (0)20 7685 2683 E [email protected] 40 Membership Q&A Design Ian Atherton, Corbicula Design (www.corbiculadesign.co.uk) Dorina Timofte tells us about her career. Printed by Charlesworth Press, Wakefield 42 We are the Champions © 2016 Microbiology Society ISSN 1464-0570 Champions scheme update. The views expressed by contributors do not necessarily reflect official policy of the Society; nor can 44 Honorary Archivist the claims of advertisers be guaranteed. Introducing archivist, Gilbert Shama. 45 Best of the blog FSC Logo Microbial stories from Uganda to the Antarctic. 47 Comment – Pathogen genomics into practice: from promising research to real Coloured scanning electron health impact micrograph of conidiophores of the Sowmiya Moorthie and Leila Luheshi fungus Aspergillus sp. Microfield Sharing data while maintaining standards and privacy. Scientific Ltd/Science Photo Library Council 2016

Executive Officers President – Professor Neil Gow College of Life Sciences and Medicine, Institute of Medical Sciences, Foresterhill, University of Aberdeen, Aberdeen AB25 2ZD; [email protected] General Secretary – Dr Evelyn M. Doyle School of Biology and Environmental Science, Science Centre West, University College Dublin, Belfield Dublin 4, Ireland; [email protected] Treasurer – Professor Chris Thomas School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT; [email protected]

Elected Members Professor Andrew Davison MRC-University of Glasgow Centre for Virus Research, Church Street, Glasgow G11 5JR; [email protected] Dr Stephen Diggle School of Life Sciences, Centre for Biomolecular Sciences, University of Nottingham, University Park, Nottingham NG7 2RD; [email protected] Professor Stephen Oliver Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA Professor David Pearce Faculty of Health and Life Sciences, Northumbria University, Northumberland Road, Newcastle-upon-Tyne NE1 8ST; [email protected] Dr Mike Skinner Section of Virology, Imperial College London, Faculty of Medicine, St Mary’s Campus, Norfolk Place, London W2 1PG; [email protected] Professor Nicola Stonehouse School of Molecular and Cellular Biology and Astbury Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT; [email protected]

Chairs of Committees Communications Committee – Dr Paul A. Hoskisson Strathclyde Institute of Pharmacy & Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE; [email protected] Finance Committee – Professor Chris Thomas See ‘Treasurer’ above Professional Development Committee – Dr David Whitworth Institute of Biological, Environmental and Rural Sciences Room S22, Cledwyn Building, Aberystwyth University, Ceredigion SY23 3FG; [email protected] Policy Committee – Dr Pat Goodwin C3 Collaborating for Health, c/o Microbiology Society, Charles Darwin House, 12 Roger Street, London WC1N 2JU Publishing Committee – Professor Charles Dorman Department of Microbiology, Moyne Institute of Preventive Medicine, Trinity College Dublin, College Green, Dublin 2, Ireland; [email protected] Scientific Conferences Committee – Dr Karen Robinson Nottingham Digestive Diseases Centre, The University of Nottingham, Nottingham NG7 2RD

4 Microbiology Today Feb 16 | www.microbiologysociety.org From the President

A Happy New Year to all of you. This is my first ‘From the President’ message. The format of this column is short so I am going to have to reign in much of my natural inclinations to tell you how excited I am to have the honour of acting as your spokesperson for the next three years. Some, but not all, of you know that I am a eukaryotic microbiologist, but I do have very broad tastes in microbiology. I hope to convince people by my actions that my approach will be team-based – and as far as I am concerned we, as Society members, are all parts of the same microbiology team.

ood teamwork is based on good considerable power and influence in our which takes place in Liverpool from communication and a sense of early career members in framing the 21 to 24 March – more details about Gbelonging to something that is future of our Society. To find out more the winners can be found in the News greater than the individual. So my open about the initiative, please read Peter section and on the Society’s website. plea is to ask you to contribute to the Cotgreave’s comments in the ‘From the The Conference will also host other discussion and the future of our Society. Chief Executive’ article. outstandingly interesting microbiological There are a number of Society The Society has redrafted its presentations and there is still ample initiatives I am particularly enthusiastic strategic vision to ensure it is fit for opportunity to contribute to the about. In a previous role at another purpose and is relevant, succinct and meeting via an offered paper or poster society I put my shoulder behind clear. This vision remains faithful to presentation. Delegates can register establishing a powerful new forum for the original remit for the Society, set online and read the Conferences pages in members at the early stages of their out by Alexander Fleming to promote this issue to find out more about what’s career. We were rewarded for this in microbiology and the interactions planned for the Annual Conference and many ways – increased membership, between microbiologists, but like the the Society’s 2016 Focused Meetings. better, more appropriate decision- microbes we study, it is also constantly The Society runs elections each year making, engagement with members at evolving. We have refined four strategic for positions on its Council, Committees an earlier stage, and investment in the pillars: International, Membership, and Divisions (and the new ECM Forum). society’s future and sustainability. It is Engagement and Knowledge Transfer, Being part of these governing bodies therefore gratifying to take up office at a and Sustainability. Within that frame gives members the opportunity to time when the Microbiology Society has our strategic priorities remain largely influence the decisions and direction already started to create the Early Career unchanged and we will use our collective of the Society, and to contribute to the Microbiologists’ (ECM) Forum. expertise to ensure that our resources fantastic projects and activities the This Forum will be involved in stimulate research, public awareness and Society produces in support of the activities to ensure that matters policy-making as effectively as possible. microbiology community. Please go to our of importance to early career In this context the theme of this website for a list of openings, and help microbiologists are fully embedded and issue is ‘Fungal Diseases’. To coincide, our determination to get full engagement addressed across the Society, from our the Society will be publishing a briefing from our members by nominating those journals through to the conferences on serious Human Fungal Diseases that who would like to make a contribution to programme. From January 2016 will be distributed to parliamentarians the running of the Society. everyone from a qualifying membership and policy-makers. constituency will be invited to join – if My personal congratulations to the Neil Gow you have not received an invite but feel winners of the Annual Conference 2016 President you qualify, please let us know. Be clear prizes, all of whom will be giving their [email protected] about this – the Forum will entrust Prize Lectures at our Annual Conference,

Microbiology Today Feb 16 | www.microbiologysociety.org 5 From the Chief Executive

One of my favourite parts of working for the Microbiology Society is meeting the wide range of members in universities, charities, industry and public service, studying every type of microbe in a myriad of different situations. It is obvious that many of you at the early stages of your careers could play a bigger role in shaping the future of the Society if we had the structures in place to facilitate it. So we have established the Early Career Microbiologists’ Forum, to give you not just a voice but real influence and decision-making power.

he Early Career Microbiologists’ similar career stage will be invited to and perfecting a very wide range of Forum will be a vehicle for those join the Forum. At the Annual Conference skills that are transferrable to other Tmembers who are embarking on in March, the Society’s new President, situations. Here are just a few: report their careers to do several things. You Professor Neil Gow, will officially launch writing, giving presentations and other will be able to meet, share experiences the Forum, and then early career communication skills; networking; group and learn from one another. You can members will elect their own Executive and team working; ethics, regulation and get involved with activities across the Committee over the spring. The Chair of governance; project management; critical organisation, including conferences, the Executive Committee will be a full thinking; risk assessment; fundraising professional development, policy work member of the Society’s Council, and and financial management; teaching and and publishing. Most importantly, your the other members of the Executive training others; succession planning; not enthusiasm, ideas and innovation will Committee will sit on the relevant to mention workplace politics. We want help shape the Society’s programmes. major committees. Only by making the to give you a chance to use these skills We will have better meetings, more Forum a fully integrated part of the in ways that develop your own careers impactful events and more widely read Society’s governance structure can we at the same time as strengthening the publications because we will be drawing guarantee that we really strengthen Society’s activities on behalf of our much more heavily than we do at the organisation for the future. So this members. present on the ideas of undergraduates, is a real chance to get involved in the The Early Career Microbiologists’ postgraduate students, postdocs and governance of the Society, to make sure Forum is new, and it will no doubt other early career microbiologists. our activities cater to the needs of develop, evolve and improve. To help Everybody knows that in any early career microbiologists. As the it do so, we need to know what members university research laboratory, the Forum evolves, it will become central want and how we can support your students and postdocs are major engines to helping us to plan conferences, careers. If you have any thoughts or of progress. Their professors are all too improve our professional development ideas, please let me know, or invite busy sitting on committees. The same programmes, and grow our outreach me to come to your lab to meet the kind of picture is often true in industry, and communications activities. students, postdocs or other early career the health service and charities. The More established members need researchers, to hear directly from you Microbiology Society wants to draw on not worry; we will not be neglecting how the Microbiology Society can this pattern, and ensure that we too can you. We are already examining ways help to connect and empower your harness the passion that early career to enhance our communications and communities. members display for microbiology in interactions with Full Members and all its variety. Honorary Members. Peter Cotgreave At the beginning of the year, Although they do not always Chief Executive every member who is an undergraduate, realise it, people in the early stages of a [email protected] a postgraduate, a postdoc or is in a scientific career are learning, practising

6 Microbiology Today Feb 16 | www.microbiologysociety.org News

2016 events New for 2016: Forum for early career members The following Society events are taking The Society is establishing a forum for student and early career members of place this year: the Society, as part of a full programme of activities and resources to support • Annual Conference 2016, the professional development of its members. If you’re an undergraduate or 21–24 March 2016, ACC, Liverpool postgraduate student member you will be invited to join, as will postdoctoral researchers and other early career members of the Society. • Focused Meeting: Molecular Biology of Archaea 5, 1–3 August To steer the Forum, we’ll be putting together an Executive Committee with roles 2016, London School of Hygiene and that bring an early career viewpoint to all of our different streams of work, from Tropical Medicine, UK conference content to policy work: • Focused Meeting: Molecular • Chair: will work with Council and the Professional Development Biology and Pathogenesis of Avian Committee. Viruses, 27–29 September 2016, • Chair-Elect: will work with the Professional Development Committee, which Charles Darwin House, London, UK oversees Professional Development at the Society. See pages 30–33 for more details. • Treasurer: will look after the financial responsibilities of the Forum. • Conferences Representative: will work with the Scientific Conferences Antifungal resistance Committee, which considers the scientific content of Society meetings. parliamentary briefing • Programmes Representative: will work with the Policy and Publishing The Society will be raising the important Committees, which look after the Society’s impact in the policy arena and issue of antifungal resistance with oversee journal publications, respectively. policy-makers later this month, with the • Communications Representative: will work with the Communications publication of our latest parliamentary Committee, which looks after Microbiology Today, Education and Outreach, briefing. The briefing will provide an and the Society’s other communications outlets. overview of the challenges posed by • International Representative: will work with the International Working Group, antifungal resistance and highlight which ensures the Society is considering its international endeavours. research being undertaken by To find out more about the Forum and each role, make sure you attend our microbiologists to tackle this problem. information session at the Annual Conference at 1.30pm on Monday 21 March The Society distributes a series 2016. of policy briefings to UK and Irish Positions on the Executive Committee will be open to election by members of the parliamentarians throughout the Early Career Microbiologists’ Forum in Spring 2016, so if you’re interested in having year to provide expert information on an impact on the work of the Microbiology Society, put yourself forward! current issues and to raise the profile of microbiology. Recent briefings include Deaths Microbiology and Climate Change and We are sad to announce the deaths of the following members. Food Security from the Soil Microbiome. The briefings are also a great resource Professor David Greenwood, who joined the Society in 1970. for teachers and students. Briefings Professor John Michael Thresh, who joined the Society in 1969. can be downloaded here: www. Please contact [email protected] if you wish to notify the Society of microbiologysociety.org/briefings the death of a member whose details can be included in this section.

Microbiology Today Feb 16 | www.microbiologysociety.org 7 Small World Initiative applications open! Upcoming grant deadlines After the Society’s successful Small World Initiative Date Grant Notes undergraduate and school partnership programmes in 1 March Travel Grants For conferences and courses 2015, we would like to invite members to apply for the 2016 from 1 April onwards*. Also for 2016 programmes. Applications are now open to run either members not eligible for Society an undergraduate programme or a school partnership Conference Grants to apply for support to present at the Annual programme, or you can apply for both! There is huge scope to Conference use the programme in whichever way fits into your teaching 15 March Microbiology in For School Members looking for and course structure, from standalone modules, embedding 2016 Schools Fund funding for microbiology teaching into the curriculum, or as an extra activity for students. initiatives taking place on or after Teachers and technicians at the Association of Science 1 May 2016 Education conference in January were also given a practical 1 April Research Visit For visits and events from 2016 Grants 1 June 2016 onwards taster session of what the Small World Initiative entails. International Both programmes involve students looking for antibacterial Development Fund compounds in soil samples, and emphasise a more realistic Education and research experience. Details of both programmes are Outreach Grants available at www.microbiologysociety.org/smallworld The Society has also been out and about collecting soil Rolling application samples from well-known sites. You may have seen our Local Microbiology Event Sponsorship – all members can apply news story about Professor Nigel Brown and four-year- for funds to support microbiology-related events, e.g. sponsored old Rory Spence collecting at 10 Downing Street in the talks. summer. Professor Melanie Welham, Executive Director of *Please note, you do not need to have received confirmation of Science at BBSRC, and Dr Simon Kerley, Head of Terrestrial abstract acceptance to apply for these grants as conditional offers Sciences at NERC, collected a soil sample from Polaris will be made. In this case, evidence of acceptance is required to claim your grant. House, home of the Research Councils, later on in the year. We will be continuing to collect samples from sites of 2016 Prize winners interest throughout 2016, and the results can be seen on our Facebook page: www.facebook.com/smallworldscience The Society is delighted to announce our 2016 Prize winners, recognising significant contributions to the field of microbiology. Microbial Genomics – call for papers All of our winners will deliver their Prize Lectures between The Society’s newest journal, Microbial Genomics (MGen) 21 and 24 March at the Society’s Annual Conference 2016. invites submissions that use genomic approaches This year’s winners are: to further our understanding of microbiology, from Prize Medal clinically important pathogens to microbial life in diverse Professor Philippe Sansonetti from the Pasteur Institute and the ecosystems. The scope covers all of microbiology, Collège de France including microbial evolution, population genomics Marjory Stephenson Prize and phylogeography, outbreaks and epidemiological Professor Steve Oliver from the University of Cambridge investigations, impact of climate or changing niche, Colworth Prize metagenomic and whole transcriptome studies, and Professor Gurdyal ‘Del’ Besra from the University of Birmingham bioinformatic analysis. The international Editorial Board is led by Co-Editors-in-Chief, Professors Stephen Bentley Peter Wildy Prize and Nicholas Thomson, from the Wellcome Trust Sanger Professor Wendy Barclay from Imperial College London Institute, UK. MGen is fully open access and article Fleming Prize processing charges are currently being waived during the Dr David Grainger from the University of Birmingham launch period. Browse the latest articles and find out how Keep an eye on the Society’s website over the forthcoming to submit at mgen.microbiologyresearch.org weeks for interviews with the winners about their research.

8 Microbiology Today Feb 16 | www.microbiologysociety.org The Society joined with British Society for Help shape the future of your Society Antimicrobial Chemotherapy for schools event at In March, nominations to Society Council, Committee FIS 2015 and Divisions will open, including positions on the new Early Career Microbiologists’ Forum! Participation in As part of the hugely successful FIS conference in Glasgow in the Society’s activities offers an exceptional opportunity November 2015, the Microbiology Society and the British Society for to develop professional and personal skills, gain new Antimicrobial Chemotherapy (BSAC) organised a joint primary school experiences and contribute to the voice and direction event at the Glasgow Science Centre with 95 Primary 7 students of the Society. attending from two local schools. They all had the opportunity to do a DNA extraction from Escherichia coli while discussing how to look for If you are interested in making a difference and committed to shaping your Society, check the genes relevant to antibiotic production and resistance, thanks to John governance pages on our website for full details on Schollar from the National Centre for Biotechnology Education. They vacancies and information on how to apply. also looked at antibiotic-producing Streptomyces on agar plates, provided by Dr Paul Hoskisson and assisted by Society member Sarah The Society welcomes contributions and Brozio, as well as taking part in a series of activities from the E-Bug feedback from members. Please contact project run by Public Health England. After a welcoming and fun [email protected] with ideas. introduction by Professor Nigel Brown, who chaired the session in the auditorium, the students then listened to two inspiring talks by Dr Benjamin Thompson William Malcolm from Health Protection Scotland and Dr Paul Hoskisson Head of Communications from the University of Strathclyde, followed by a Q&A session. [email protected]

Microbiology Today Feb 16 | www.microbiologysociety.org 9 Mycotoxins,

food security and

climate change: do we know enough?“

Coloured scanning electron micrograph of Penicillium chrysogenum showing conidia being extruded from a Naresh Magan and Angel Medina conidiophore. Dr Jeremy Burgess/Science Photo Library

Importance of moulds One man’s pharmaceutical metabolite is another man’s mycotoxin Filamentous fungi are ubiquitous in the environment. They produce millions and animal diseases. Their spores are flavus. This stimulated scientific of spores that allow them to colonise responsible for human allergies, cause research into this area, with the almost all natural habitats. Indeed, plant diseases and attack man-made term mycotoxins coined for any toxic they are essential components of the materials, especially building materials secondary metabolite, naturally produced cycling of nutrients in the environment. “under damp conditions. Who has not by fungi. Subsequently, aflatoxins were They can produce a battery of heard of athlete’s foot, thrush, dry rot, shown to be the most toxic naturally- enzymes that allow them to colonise or observed the rapid fungal decay of produced compound in food and were surfaces including humans, animals, woody materials? classified as a class 1A carcinogen by food and building fabric. They have the International Agency for Research both positive and negative impacts Discovery of mycotoxins on Cancer. Thus, the turkey chicks had on our daily lives. On the one hand, and their importance probably died from liver failure. This they have been utilised successfully In the early 1960s, the death of resulted in a surge of interest to discover for the production of antibiotics, hundreds of thousands of turkey chicks whether other mycotoxins naturally pharmaceutical metabolites, industrially prior to Christmas resulted in an produced by moulds might be present in and medically useful enzymes and, of investigation of the probable causes. different food commodities. course, as food. Mushroom production The turkey feed was identified as the Over the last five decades, it has is probably the most successful and culprit and, after chemical analysis, been shown that cereals, nuts, spices, economically important exploitation of it was shown that certain secondary dried fruits, coffee, cocoa, fruit juices, filamentous fungi. On the other hand, metabolites produced by a contaminant grapes and red wine may all contain both yeasts and filamentous fungi are filamentous fungus were toxic, and mycotoxins produced by filamentous responsible for significant economic aflatoxin was identified. The fungus moulds under warm and humid losses because they cause human responsible was found to be Aspergillus conditions. The mycotoxins of

10 Microbiology Today Feb 16 | www.microbiologysociety.org importance from a food safety

perspective include aflatoxins (B1, B2,

G1, G2 and M1), ochratoxin A, patulin,

fumonisins (B1, B2, B3), type A (T-2 and HT-2 toxin) and type B trichothecenes (deoxynivalenol and its derivatives, nivalenol) and zearalenone. They are very heat stable and survive processing, and thus are very difficult to destroy. These mycotoxins are produced by Aspergillus, Penicillium and Fusarium species. They have attracted attention because of their adverse health effects on humans and animals. Aflatoxins,

especially aflatoxin B1, is genotoxic, i.e. can damage DNA, and causes liver cancer in humans and animals. The most recent serious outbreak reported Coloured scanning electron micrograph of Penicillium chrysogenum showing conidia being extruded from a is of school children in rural Kenya who conidiophore. Dr Jeremy Burgess/Science Photo Library had consumed mouldy maize. This resulted in about 150 fatalities and up to 500 children being hospitalised because of acute exposure to aflatoxins. Other mycotoxins have a range of health effects including kidney damage, gastrointestinal impacts, reproductive disorders or suppression of the immune system. The WHO/JECFA committee has used available data to establish a tolerable daily intake (TDI) level. This is an estimate of the quantity of mycotoxin that someone can be exposed to daily over a lifetime without it having a significant risk to health. The intake of raw or processed food commodities will vary in different regions of the world. For example, maize is a staple food in parts of Africa, while in Europe it may be used predominantly as a small part of the daily diet. Thus, in terms of consumer safety, this complicates the exposure assessments. The European Union has the strictest legislative limits worldwide for mycotoxins (see Table 1). This affects food production within the EU and imports from other countries.

Microbiology Today Feb 16 | www.microbiologysociety.org 11 Indeed, it has been shown that in 2014, species (Aspergillus, Penicillum and been shown that storage under marginal at the EU borders, from the overall Fusarium), as it can provide the platform conditions, which allow these toxic rejections of food/feed commodities for for minimisation strategies. This type moulds to grow, will cause quality and human and animal use, 35% were due of data has been used to dry and store nutritional losses, as well as result in to mycotoxin contamination levels above food/feed commodities under conditions rejection for food use. Often, only a small the legislative limits (Rapid Alert System which do not allow colonisation and change in dry matter (<0.5%) can result for Food and Feed, RASFF). mycotoxin contamination by these in contamination with mycotoxins above moulds, especially during storage and the legislative limits. Minimising strategies subsequent downstream processing, The problem of mycotoxins varies The development of minimisation or e.g. flour, pasta, fruit juice, dried fruit, nut with season and is very unpredictable prevention strategies has focused products, coffee and cocoa processing. in temperate regions of the world. Thus research on mycotoxins for many Minimisation strategies have integrated approaches to combine decades. These have to be considered included the use of relatively resistant different types of environmental and in the context of the production of cultivars (where available), effective crop data, pre-harvest and post-harvest, many food/feed commodities in pre-harvest Good Agricultural Practices, have now been taken to try and provide tropical and sub-tropical climatic timing of application of chemical or an early warning of the relative risk of regions. The temperatures and relative biological control treatments for pests/ specific mycotoxins, to try and minimise humidities are conducive to the growth fungal infection, and prevailing weather contamination in food and feed chains. of mycotoxigenic moulds and toxin conditions. Hygiene issues, in relation contamination during pre-harvest to both pests and mould contamination, Climate change, food security growth of crops and post-harvest, where are critical during medium and long- and mycotoxins drying and storage are relatively difficult term storage and during transport of There are many reports which have to manage. While prevention is better food/feed commodities. In a global shown that predicted changes in than cure, this is often very difficult in market, these are transported over long weather patterns in different regions such environments. distances through different climatic of the world will impact on agricultural It is important to understand conditions. Many food products are sustainability. For example, in Europe, the optimum and marginal boundary hygroscopic and can easily absorb water southern Europe is considered to be a conditions of temperature and relative and allow mycotoxigenic moulds to grow, hot spot for climate change (CC), where

humidity for growth and mycotoxin and perhaps increase contamination combined changes of elevated CO2 (x2 production, especially by the key and compromise quality. It has also existing levels), increases in temperature (+2–4oC) and rainfall/drought extremes Table 1. Important commodities for which EU legislative limits exist will have negative effects on food

Aflatoxin Ochratoxin A (OTA) Patulin Fusarium toxins production. Similar impacts are expected Groundnuts + + in parts of North and South America, Nuts + + e.g. Brazil, and Africa and Asia. This Dried fruit + + could compromise food security and Cereals + + + availability. Maize + + + A report by the European Food Spices + + Safety Authority (2012) showed that Baby foods + + + + cereal crops will ripen much earlier in Coffee + the season in the future than at present Cocoa + and this could result in the potential Grape juice + for additional impacts of pests and Fruit + + + (apple) diseases, which could increase the Milk, egg + prevalence of mycotoxin contamination Wine + and affect yields and cereal quality.

12 Microbiology Today Feb 16 | www.microbiologysociety.org J R Soc Interface 9, 757–767. Battilani, P. & others (2012). Modelling, predicting and mapping the emergence of aflatoxins in cereals in the EU due to climate change. www.efsa.europa.eu/en/supporting/ pub/223e Bebber, D. P., Ramotowski, M. A. T. & Gurr, S. J. (2013). Crop pests and pathogens move poleward in a warming world. Nat Clim Change 3, 985–988. Bebber, D. P., Holmes, T. & Gurr, S. J. (2014). The global spread of crop pests and pathogens. Global Ecol Biogeogr 23, 1398–1407. Medina, A. & others (2013). Integrating toxin Coloured scanning electron micrograph of the common soil-dwelling fungus Aspergillus flavus. gene expression, growth and fumonisin B1 Manfred Kage/Science Photo Library and B2 production by a strain of Fusarium Indeed, in southern Europe and the This will be linked to increased verticillioides under different environmental Balkans, extremely hot summers have mycotoxin contamination due to factors. J R Soc Interface 10, 1742–1762. already resulted in changes in the maize increased pest damage. Increased doi:10.1098/rsif.2013.0320. cultivation ecosystems, resulting in a contamination levels may occur of Medina, A. & others (2015). Climate change switch from contamination with Fusarium existing mycotoxins, or emigration of factors and A. flavus: effects on gene species and fumonisin mycotoxins to other mycotoxins may occur to new expression, growth and aflatoxin production. A. flavus and aflatoxin contamination, regions where they were not previously World Mycotoxin J 8, 171–179. which exhibits a much higher toxicity. prevalent. Potential also exists for Medina A., Rodriguez, A. & Magan, N. (2014). This has impacted on feed quality and the new mycotoxins occurring for the first Effect of climate change on Aspergillus flavus risk of entry of aflatoxin 1M (a conversion time because of extreme stress of CC. and aflatoxins. Front Microbiol 5, doi:10.3389/ product of aflatoxin 1B from feed) into This could have profound impacts on fmicb.2014.00348. milk and thus the dairy production chains. food sustainability in many regions of Medina, A., Rodriguez, A. & Magan, N. (2015a). Recent studies at Cranfield University the world, with developing countries Changes in environmental factors driven by suggest that under CC conditions, A. flavus taking the brunt of the impacts, climate change: effects on the ecophysiology will grow in a similar way on maize- possibly resulting in negative social of mycotoxigenic fungi. In Climate change and based substrates or maize grain but that consequences. Mycotoxins, Edited by L. M. Botana & M. J. aflatoxin 1B production will be stimulated. Sainz. Berlin: De Gruyter. This could have profound implications of Naresh Magan and Angel Medina Medina, A., Rodriguez, A. & Magan, N. (2015b). mycotoxin contamination of cereals. Applied Mycology Group, AgriFood Climate change and mycotoxigenic fungi: Recent global predictions suggest Theme, Cranfield University, Cranfield, impacts on mycotoxin production. Curr Opin that pests and fungal pathogens are Bedfordshire MK43 0AL, UK Food Sci 5, 99–104. moving at the rate of 5–6 km per year [email protected] Vary, Z. & others (2015). The severity of wheat from the equator to the poles. In addition, [email protected] diseases increases when plants and pathogens the diversity of pests and diseases will are aclimatised to elevated carbon dioxide. increase, impacting on sustainable Further reading Global Change Biol 21, 2661–2669. food production. Under these new Abdel-Hadi & others (2012). A systems Vaughan, M. M. & others (2014). Effects approach to model the relationship conditions, there are risks of mycotoxin of elevated CO2 on maize defence against contamination increasing in certain between aflatoxin gene cluster expression, mycotoxigenic Fusarium verticillioides. Plant regions which are considered to be environmental factors, growth and Cell Environ 37, 2691–2706. ‘bread baskets’ for food production. toxin production by Aspergillus flavus.

Microbiology Today Feb 16 | www.microbiologysociety.org 13 A plague on our ashes

Anne Edwards and J. Allan Downie

In late autumn 2012, it became evident that ash dieback disease had become established in native woodlands in the eastern regions of the UK. This was the leading edge of an epidemic that had already swept east to west across mainland Europe over a period of about 20 years.

14 Microbiology Today Feb 16 | www.microbiologysociety.org e were aware of the this iconic tree may disappear from our they release highly infective ascospores disease because of our landscape. (around 1,500 per hour every morning Winvolvement in helping in summer months) and the whole cycle manage Ashwellthorpe Lower Wood, A new pathogen in Europe starts again. an ancient coppiced woodland in South What was already known about the Normally, trees rid themselves Norfolk. This woodland, owned by the disease-causing fungus? Scientists of the saprophyte H. albidus in autumn Norfolk Wildlife Trust, is a Site of Special from across Europe had established with leaf fall. However, H. fraxineus Scientific Interest (SSSI) and its name, that Chalara fraxinea is the vegetative grows faster and more aggressively Ashwellthorpe, comes from the Vikings, (anamorphic) form of the fungus, which on ash trees and so, rather than being for whom the ash (Fraxinus excelsior) kills trees by invading stems and trunks contained within the leaves and leaf was sacred. It was devastating to see and blocking the vasculature. The stems, H. fraxineus can grow into young coppiced regrowth showing early fungus also has a sexual form, which the woody parts of the tree. There it signs of what looked like ash dieback. was originally named Hymenoscyphus continues to grow slowly over winter Since this occurred just a few miles from pseudoalbidus, because it looked and then in spring probably grows where we work at the John Innes Centre similar to, and has the same host as, rapidly as the tree starts to initiate new (which specialises in plant and microbial Hymenoscyphus albidus, which grows leaf growth. This rapid fungal growth in research), we asked ourselves and our widely (but non-pathogenically) on ash the phloem and xylem of branches can colleagues what we could do to help an trees across Europe. Due to its distinctive then strangle the growth of the distal iconic native tree. characteristics, the pathogen was young leaves, causing the characteristic As a first step, we extracted and renamed Hymenoscyphus fraxineus, and ‘dieback’ symptoms. tested DNA from infected branches we now know that where the disease Had the harmless native and our fears were confirmed: the is present, H. fraxineus is completely saprophyte turned into a killer or was trees were infected with the fungus displacing H. albidus. Both species live the destructive H. fraxineus itself a Chalara fraxinea, the causal agent of in ash leaf litter and spread by releasing saprophyte which had found itself in a ash dieback. Symptoms of the disease sexual (haploid) spores into the air and foreign environment without its natural include the wilting (dieback) of young infecting surrounding trees. Spores fired host? The latter theory gained popularity leaves in spring, dying of leaves in late upwards from fruiting bodies land on when it was found that Asian ash summer while they are still attached to ash leaves, germinate and penetrate as species such as Fraxinus mandschurica the tree, lesions and cankers on stems the vegetative form into the petiole and were unaffected by ash dieback. and branches, and dieback of the crown. main leaf stem (rachis). When the Genome sequencing has revealed that Young saplings and coppice regrowth rachis falls, it takes the fungi with it H. fraxineus has a considerably larger can succumb quite rapidly, some within and sometime during the winter and genome (60 megabases) than the one growing season. Older trees can following spring, the fungi enter the saprophyte H. albidus (40 megabases) survive an initial attack but many stop sexual phase of the lifecycle. Pre-fruiting and so these are two related but rather growing and may become prone to structures start to appear, some of different species. It is probable that H. secondary infections. In other parts of which develop into tiny white cup- fraxineus was introduced into Eastern Europe, over 90% of the ash trees were shaped mushrooms (ascocarps) less Europe, possibly due to movement of killed or severely affected by the disease, than 0.5 cm wide. There can be 20 of trees or leaves from somewhere in East so there was an outcry in the UK as the these mushrooms on a single petiole Asia, where F. mandschurica is adapted general public and media realised that and when they mature in summer, to growth with H. fraxineus.

Scanning electron micrograph of the wood of an ash tree (Fraxinus excelsior) showing xylem tracheids. Power and Syred/Science Photo Library

Microbiology Today Feb 16 | www.microbiologysociety.org 15 Genetic tolerance in ash trees F. excelsior can respond in different ways when challenged by H. fraxineus. Many trees appear to be exceptionally sensitive, dying within a few years of infection; a few others (about 5% in Denmark) seem to be much more tolerant to the disease. In between these two extremes, there is a range of responses. Danish scientists had grown several clones of grafted trees in many different environments and fortuitously a couple of these showed some tolerance (one high and one intermediate) to the disease. Since this tolerance was consistently observed in various locations and in different environments, it could be concluded that the tolerance was genetically determined.

Genomics of host and pathogen With funding from the BBSRC and Defra, a research consortium called Nornex (http://nornex.org/) was set up including groups from the John Innes Centre, The Sainsbury Laboratory and The Genome Analysis Centre (all in Norwich), the Universities of Exeter, Edinburgh and York, FERA, Forest Research, the University of Copenhagen, and the Norwegian Forest and Landscape Institute. The aims were to (a) use genomics-based tools to establish a foundation of knowledge on the pathogen, (b) establish laboratory- based tests of pathogenicity and assays of growth and survival of the pathogen, and (c) use genomics and transcriptome- based approaches in ash trees to try to map tolerance (resistance) to the disease. These aims were underpinned by a desire to try to take a different approach and use an open access and Coloured scanning electron micrograph of a fruiting body of the fungus Chalara fraxinea (Hymenoscyphus crowdsourcing approach. As part of that, pseudoalbidus), the causal agent of ash dieback. Crown © Courtesy of FERA/Science Photo Library

16 Microbiology Today Feb 16 | www.microbiologysociety.org “

that the original H. fraxineus came from We have preliminary data from the sequencing of tree leaf RNA, Asia. We have preliminary data from the identifying potential genetic markers that could be associated with sequencing of tree leaf RNA, identifying potential genetic markers that could be inheritance of tolerance to the disease. associated with inheritance of tolerance to the disease. We believe that we a website called openashdieback (http:// (INDELs) can be identified and further have established a framework that will oadb.tsl.ac.uk/) was established to host studied in relation to alterations in, for enable us to predict which trees will be new observations and provide access example, pathogenicity. tolerant to the disease, to understand to data generated by the consortium. the nature and diversity of the pathogen, In view of the intense public interest, The research and to carry out laboratory-based we also developed and released Three years on and what has been tests of pathogenicity in tree seedlings. Fraxinus, a Facebook-based citizen achieved? We have a good genome All of these can be used to rebuild a science genomics-based game (https:// sequence of H. fraxineus, revealing that genetically diverse population of trees apps.facebook.com/fraxinusgame/). it does not contain the great diversity tolerant to this disease that, over time, This enabled non-specialists to of genes for wood degradation like will probably kill or severely damage contribute to the genomic studies of those used by wood-rotting fungi, but 80–90% of the UK ash tree population. “the pathogen by helping to improve it does possess cell wall-degrading genetic variant predictions from DNA enzymes such as cellulases and pectate Anne Edwards and J. Allan Downie sequence alignments. Many computer lyases used for cellular penetration. John Innes Centre, Norwich Research programs have been devised to optimise It also synthesises toxins, effectors Park, Norwich NR4 7UH, UK alignments. However, none can improve and predicted protein inhibitors to [email protected] on the pattern recognition skills of the help it evade plant defences. Genome [email protected] human eye. Once an alignment process sequencing of different isolates has is complete, genetic variations such as revealed that there is less genetic Further reading single nucleotide polymorphisms (SNPs) diversity in European isolates than in Gross, A. & others (2012). Reproductive or insertion-deletion polymorphisms Asian isolates and it seems highly likely mode and life cycle of the ash dieback pathogen Hymenoscyphus pseudoalbidus. Fungal Genetics and Biology 49, 977–986. McKinney, L. V. & others (2011). Presence of natural genetic resistance in Fraxinus excelsior (Oleraceae) to Chalara fraxinea (Ascomycota): an emerging infectious disease. Heredity 106, 788–797. Saunders, D. & others (2014). Crowdsourced analysis of ash and ash dieback through the Open Ash Dieback project: A year 1 report on datasets and analyses contributed by a self-organising community. BioRxiv. doi:10.1101/004564. Rallapalli, G. & others (2015). Cutting edge: Lessons from Fraxinus, a crowd-sourced citizen science game in genomics. eLIFE. doi:10.7554/Elife.07460. Fraxinus, a Facebook-based citizen science genomics-based game. Anne Edwards and Allan Downie

Microbiology Today Feb 16 | www.microbiologysociety.org 17 Candida: living with a killer fungus

Coloured scanning electron micrograph of Candida Neil A. R. Gow, Ingrida Raziunaite, Fiona M. Rudkin, Katja Schaefer & Bhawna Yadav albicans. Nature’s Geometry/Science Photo Library

ecent medical advances in If you are sneezing your way the treatment of cancer, trauma, Rorgan failure, HIV and other conditions save many people who years through winter and wondering ago would not have survived. These are the new group of patients who whether your immune system is are vulnerable to attack by killer fungi, including about a half-dozen species of functioning well, then realise that Candida, that profit from any weakness in immunity and health. These species it is at least holding at bay a fungus collectively account for the fourth highest burden of human bloodstream that colonises most of us, and kills infections (around 250,000 each year), of which as many as 40% may not more than 50,000 immunologically survive. Unfortunately, these organisms do not have a large community of vulnerable people every year. microbiologists backing up our need to know more about them. But we are gradually learning how to hit harder

18 Microbiology Today Feb 16 | www.microbiologysociety.org breached or the protective bacterial that are difficult to dislodge and are microflora is depleted. In otherwise more resistant to antifungal drugs. healthy individuals, Candida species Another risk category is those fighting can establish superficial mucosal other immunosuppressive diseases, infections called ‘thrush’ or ‘yeast such as HIV/AIDS, which has created infections’. However, patients with a vulnerable worldwide population of severely weakened immune systems millions of people who are susceptible to due to injury, surgical trauma, organ infections from Candida and other fungi, transplantation, long-term antibiotic like Cryptococcus. or chemotherapy treatment, or those Superficial infections of mucosal with inherited genetic mutations in surfaces are extremely common, protective immune signalling pathways, occurring in ~25% (~1.7 billion) of the have increased risk of developing healthy population globally. Around more severe forms of disease that 50–75% of women in their childbearing can include life-threatening invasive years suffer at least one incidence of bloodstream or systemic infections. The vulvovaginitis and 5–8% (~100 million) use of medical implants and central women have at least four thrush intravenous catheters can also lead to episodes annually. A further 10 million formation of elaborate Candida biofilms, cases of oral thrush and 2 million cases which seed bloodstream infections of oesophageal are added to the annual

Coloured scanning electron micrograph of Candida albicans. Nature’s Geometry/Science Photo Library with better drugs, to diagnose earlier and to understand the underpinning immunology of fungal infections.

The Candida conundrum Candida species are yeast-like fungi, which normally thrive as harmless commensal organisms in microbiota of the mucous membranes of the oral cavity, gastrointestinal tract or urogenital tracts and more rarely on the skin (Fig. 1). Typically, around 50% of us are colonised at any one time without any noticeable clinical symptoms. However, these organisms are also extremely serious opportunistic pathogens that cause infections when the immune system is compromised, immune barriers are Fig. 1. Cultivation of yeast cells of Candida albicans in the laboratory. Neil Gow

Microbiology Today Feb 16 | www.microbiologysociety.org 19 affected by invasive candidiasis, and Oral candidasis mortality (up to 37–44%) remains high Eye infections despite the availability of antifungal Cerebral candidasis drugs.

Hot topics in research Lung abscess At the time of writing, more than 1,300 papers were published on Candida in 2015 alone. This high research activity in the field is yielding Gut commensal fascinating new insights into these Surgical transmigration Hepatic abscess pathogens. Human genomics has revealed mutations in human genes Renal abscess such as dectin-1, CARD9, AIRE, Pyelonephritis IL-12R, STAT1, STAT3, which contribute Candiduria to susceptibility to Candida infections. Vulvovaginitis These observations help us understand the signalling pathways that govern Mucosal and antifungal immunity. A major recent dermatological discovery has been the first example of a candidasis membrane pore-forming toxin of Candida called Ece1 that helps explain why the hyphae of Candida albicans cause Osteomyelitis tissue damage. We are beginning to learn how Candida in the gut contributes to the immunomodulatory influence of the gut microbiome and how the Implants fungus adapts during human infection Medical devices and sidesteps immune surveillance. It was shown recently, for example, that Candida albicans generates a specialised GUT form that is adapted Nail infections for commensal carriage in the intestine. We are also beginning to understand why our immune systems struggle to keep up with Candida infections because its cell wall constantly changes its Fig. 2. Clinical manifestations of Candida disease at different body sites.With thanks to Prashant Sood surface properties and is therefore a disease burden by HIV/AIDS organs of the human body, leading moving target for our phagocytic white and other mitigating factors. Although to life-threatening invasive organ blood cells. Next generation genome less frequent than superficial infections, failure and pathological immuno- sequencing, and a constantly improving invasive fungal infections have high inflammation (Fig. 2). Annually, set of genetic tools including CRISPR mortality rates, often worse than those candidaemia causes more than 50,000 Cas9, are making our knowledge of of bacterial and viral diseases. During deaths and is the fourth most common the connections between the Candida these systemic infections, Candida has cause of bloodstream infections. More genotype and (pathogenic) phenotype the potential of colonising almost all than 250,000 people worldwide are ever more accessible.

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“

The development of diagnostic tests which are cheap and portable to low-income countries in field hospital conditions is urgently required.

Future prospects – biotechnology companies rather than global burden of fungal infections making a difference Big Pharma, and the focus of their work and make inroads to the rather grim Diagnosing invasive Candida infection has been mainly, but not exclusively, on statistics relating to candidiasis and is challenging because symptoms are improving the efficacy and half-life of medical mycology in general. often non-specific. Current methods already approved classes of antifungal rely primarily on blood culture, which drugs. In 2015, two new antifungals have Neil A. R. Gow, Ingrida Raziunaite, is slow and of limited sensitivity. PCR, emerged – an echinocandin (CD101 IV Fiona M. Rudkin, Katja Schaefer & “ [Biafungin] – under development for serological and proteomic-based Bhawna Yadav methods have been a valuable addition Candida) and new triazole (isavuconazole The Aberdeen Fungal Group, to diagnostics in reducing sample – now licenced by the FDA and in Europe Institute of Medical Sciences, turnaround time and increasing for Aspergillus and Mucor), both with University of Aberdeen, Aberdeen sensitivity. However, these methods improved clinical characteristics in AB25 2ZD, UK do not always discriminate Candida various patient settings. Of course, it [email protected] colonisation and invasion. Because late would be extremely valuable to be able diagnosis equates to a poor prognosis, to prevent infection through vaccination Further reading the focus on improving diagnostics is a of vulnerable patients. However, Brown, G. D. & others (2012). Human clinical need as important as generating research into fungal vaccines has fungal infections: the hidden killers. Science new antifungal drugs. In addition, the lagged behind that of other pathogens Translational Medicine 4, 165rv13. development of diagnostic tests which and there are currently no antifungal Brown, A. J. P., Brown, G. D. & Gow, N. A. R. are cheap and portable to low-income vaccines approved for clinical use. (2014). Metabolic modulation of Candida countries in field hospital conditions A new generation of experimental immunogenicity and pathogenicity. Trends in is urgently required. vaccines based on Candida-specific Microbiology 22, 614–622. Disappointingly, the recent and pan-fungal cell wall components Butler, G., Lorenz, M. & Gow, N. A. R. (2012). introduction of new antifungal therapies are beginning clinical trials. Two of Evolution and genomics of the pathogenic has only had a relatively minor impact these target recurrent vaginal Candida Candida species complex. In Evolution of on the mortality rates associated with infections (NDV-3 [Novadigm] and Virulence in Eukaryotic Microbes, pp. 404–424. invasive candidiasis. This is in part a PEV-7 [Pevion]), and several others have Edited by B. J. Howlett, J. Heitman & L. D. knock-on effect of suboptimal diagnostic shown efficacy in pre-clinical animal Sibley. Wiley-Blackwell. testing together with drug-associated models of infection. In addition, novel Kullberg B.-J. & Arendrup, M. (2015). Invasive limitations such as emergence immunotherapies which boost antifungal Candidiasis. New England Journal of Medicine. of resistance, toxicity, drug–drug immune competence may be part of 373,1445–1456. interactions and problems in the route future options in antifungal treatment. Netea M. G. & others (2015). Immune defence of drug administration. At present, the As we move forward, addressing these against Candida fungal infections. Nature pipeline of new antifungals is being research areas is likely to be of upmost Reviews Immunology. doi:10.1038/nri3897 developed by predominately smaller importance if we are to reduce the

Microbiology Today Feb 16 | www.microbiologysociety.org 21 Coloured transmission electron micrograph of Cryptococcus neoformans, the cause of cryptococcosis, showing a single, circular encapsulated yeast. CNRI/Science Photo Library Human diseases caused by From fungal pathogens have long been neglected as a medical problem, but the dramatic increase in peaches immunocompromised individuals over the last 50 years, resulting to patients: both from the HIV/AIDS pandemic and more widespread use of immunosuppressive therapies, the many has led to an annual toll of over 2 million deaths due to fungal faces of infections. Additionally, over 300 million people are chronically cryptococci infected by fungi, leading to problems ranging from skin irritation to blindness. Paula I. Seoane, Rafael Schneider and Robin C. May

22 Microbiology Today Feb 16 | www.microbiologysociety.org Cryptococcus species in decaying vegetation of several tree to active yeast cells (4–10 µm), since Amongst the life-threatening fungal species. C. neoformans is also found in only small cells can penetrate so far into pathogens, Cryptococcus neoformans bird faeces, which partly explains the the lung. In most individuals this initial and its close relative Cryptococcus gattii high incidence of this species in urban pulmonary infection is rapidly contained, account for almost 1 million infections locations. but in people lacking an appropriate per year and around 650,000 deaths. immune response, the infection can Cryptococcal infections were recognised Cryptococcosis spread to the blood and central nervous as a major threat only in the 1980s Cryptococcosis results from inhalation system, causing meningoencephalitis, with the emergence of AIDS, but, in fact, of fungal cells or spores from the which is rapidly fatal without treatment. the organism had been first isolated in environment, causing subsequent The ability of these environmental 1894 by an Italian researcher, Sanfelice, lung infection. The first step to disease fungi to cause human infections is from fermented peach juice and, in the development is the arrival of fungal underpinned by a number of classical same year, from a patient with a chronic cells deep in the alveoli of the lung. virulence factors, most notably the granuloma. Consequently, desiccated yeast cells production of a polysaccharide capsule Both pathogenic Cryptococcus or spores are considered the most (Fig. 1) which protects Cryptococcus species are found in a diverse range of important infectious propagule due to from phagocytosis, and the production niches in the environment, particularly their small size (~3 µm) in comparison of melanin pigment, which protects the fungal cell from oxidative damage. Fig. 1. Cryptococcus gattii cell stained with India ink, showing capsule (red), fungal cell wall (blue) and Perhaps most remarkable, however, is the budding yeast (yellow). Bar, 5 µm. Paula Seoane, Rafael Schneider and Robin C. May the ability that cryptococci have to evade immune activation.

How does Cryptococcus evade the immune system? Normally, exposure to fungal cells triggers a potent inflammatory response. However, Cryptococcus yeast cells are remarkably immunologically inert. Not only do they fail to elicit pro- inflammatory cytokines from dendritic cells (as opposed to other fungi such as Candida albicans), they actively promote the production of anti-inflammatory cytokines such as IL-10 or IL-4. This cytokine profile enables Cryptococcus to repolarise the immune response, reducing the so-called Th1 response (a potent inflammatory and antimicrobial response, which is particularly effective in eradicating intracellular pathogens) and instead shifting towards a Th2 profile, an inflammatory state that is targeted towards large pathogens such as parasitic worms and is ineffective at removing single-celled pathogens such as cryptococci. In parallel, a

Microbiology Today Feb 16 | www.microbiologysociety.org 23 proportion of the infecting yeast cells expand dramatically in size to form giant or ‘titan’ cells. These cells are thought to arise from replication without concomitant mitosis, since they are polyploid and uninucleate, and block phagocytosis both of themselves and, interestingly, of normally-sized neighbouring cryptococci via a mechanism that Fig. 2. Cryptococcus neoformans cell (blue) being engulfed by a human macrophage (red and green). is not yet characterised. Paula Seoane, Rafael Schneider and Robin C. May

Cryptococcus and phagocytes pH and reactive oxygen species that are proinflammatory signaling, and is If these strategies all fail and the abundant in this organelle. therefore thought to pose an advantage invading fungus is engulfed by host Once established within the over lytic escape. phagocytes, cryptococci are able to phagocyte, cryptococci are able to engage an extra line of defence and replicate rapidly but can also escape the How does Cryptococcus persist as facultative intracellular macrophage via an intriguing non-lytic reach the brain tissue? pathogens (Fig. 2). Once inside the host exocytosis, also known as vomocytosis The most dangerous consequence cell, Cryptococcus cells have developed (Fig. 3). Following vomocytosis, both of cryptococcal infection is numerous mechanisms to both reduce the expelled cryptococci and the meningoencephalitis, resulting from the antimicrobial properties of the macrophage are undamaged. Thus this dissemination of the fungus to the phagosome and to neutralise the low escape mechanism ensures minimal central nervous system. To infect this immune privileged site, cryptococci (a) must exit the lungs, enter peripheral blood circulation and bypass the blood– brain barrier (BBB). It now appears that cryptococci accomplish this feat in three ways (Fig. 4). Firstly, yeast 3:20 4:35 7:50 8:30 cells can make their way through tight (b) junctions of the endothelial cells using proteases such as Mpr1, in a process called paracytosis. Secondly, yeast cells can infiltrate the BBB by transcytosis, a process that is mediated by the 0:00 4:00 7:05 12:25 interaction between hyaluronic acid (c) in the cryptococcal surface and CD44 present in the luminal endothelium, resulting in direct uptake of the fungus by endothelial cells and migration through the cell’s cytoplasm to reach 8:40 8:45 8:50 8:55 the brain tissue opposite. Finally, a third possibility involves cryptococci Fig. 3. Time-lapse images of J774 macrophages infected with GFP-tagged Cryptococcus neoformans crossing the BBB whilst concealed exemplifying intracellular replication (a), lytic escape (b) and vomocytosis (c). The time post-infection is shown within phagocytes, a so-called ‘Trojan in each panel. Paula Seoane, Rafael Schneider and Robin C. May Horse’ route. Evidence supporting this

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Blood vessel Central nervous system

Cryptococcus cell “ Trojan Horse It now appears that the high pathogenicity of this lineage results from a novel “division of labour”

Paracytosis virulence mechanism in which cryptococcal

Transcytosis cells collaborate to drive extremely rapid intracellular Blood–brain barrier proliferation and thus

Fig. 4. Cryptococci can infect the central nervous system by three routes: Trojan Horse, paracytosis or overwhelm the host. transcytosis. Paula Seoane, Rafael Schneider and Robin C. May mechanism comes from studies in mice compromising conditions. Now known “and Dr Jenson Lim for Figure 2. The where depletion of alveolar macrophages as the Pacific Northwest Outbreak, authors are supported by funding from the significantly reduced cryptococci burden this disease cluster now represents Darwin Trust of Edinburgh (P.S.), the Science in the brain tissue and direct infection the most serious outbreak of invasive Without Borders Program – CNPq (R.S.) and with Cryptococcus results in lower fungal disease in the healthy population the European Research Council (R.C.M.). dissemination to the brain than adoptive to date. It now appears that the high transfer of infected monocytes. pathogenicity of this lineage results from Paula I. Seoane and Robin C. May a novel ‘division of labour’ virulence Institute of Microbiology and Infection Cryptococcus: one genus, mechanism in which cryptococcal & School of Biosciences, University of several pathogens cells collaborate to drive extremely Birmingham, Edgbaston, Birmingham One of the most remarkable findings rapid intracellular proliferation and B15 2TT, UK of recent years has been the use of thus overwhelm the host, even in the comparative genomic/phenotypic presence of a fully functional immune Rafael Schneider studies to reveal subtle differences in response. Centro de Biotecnologia, Universidade the biology of different cryptococcal Federal do Rio Grande do Sul, Porto lineages. Typically, infections with Summary Alegre, RS 91501-970, Brazil Cryptococcus gattii, although much rarer Since its recognition as a major threat than Cryptococcus neoformans infections, to human health in the 1980s, research Further reading cause more aggressive disease on Cryptococcus has highlighted the Casadevall A., Steenbergen J. N., symptoms and respond more slowly extraordinary range of virulence factors Nosanchuk J. D. (2003). ‘Ready made’ to antifungal drugs. However, within used by this organism to drive disease. virulence and ‘dual use’ virulence factors each species certain lineages appear In particular, its ability to modulate in pathogenic environmental fungi – the to be more pathogenic than others. For host immunity and to enter the central Cryptococcus neoformans paradigm. Curr instance, the VNB lineage of Cryptococcus nervous system by hiding inside Opin Microbiol 6, 332–337. neoformans is associated with poorer macrophages has revealed unique Johnston S. A. & May R. C. (2013). patient outcomes than other strains. Most aspects of host–pathogen biology. Cryptococcus interactions with macrophages: dramatic, however, is the involvement of Intensive ongoing genetic, cell, biological evasion and manipulation of the phagosome the VGIIa lineage of Cryptococcus gattii and clinical investigations offer the by a fungal pathogen. Cell Microbiol 15, in a large cryptococcosis outbreak that prospect of us soon learning much more 403–411. started in 1999 on Vancouver Island, about this enigmatic human pathogen. Kwon-Chung & others (2014). Cryptococcus Canada. During the following decade, neoformans and Cryptococcus gattii, the 236 human cases with 19 deaths Acknowledgements etiologic agents of cryptococcosis. Cold Spring were reported, almost none of which The authors would like to thank Dr Ewa Harb Perspect Med 4, a019760. were in people with classical immune- Bielska for providing the image for Figure 1

Microbiology Today Feb 16 | www.microbiologysociety.org 25 The hidden viruses of the fungal kingdom

Paul A. Rowley Mycoviruses growing on medium. Paul Rowley

26 Microbiology Today Feb 16 | www.microbiologysociety.org processes, while mycoviruses have evolved countermeasures to subvert There are countless examples of plant, animal and bacterial them. One example of a potent antiviral viruses that cause severe symptoms of disease, sometimes mechanism within fungi is RNA interference (RNAi), which recognises with considerable socio-economic consequences. Viruses and processes mycovirus double- stranded RNAs, leading to the inhibition of fungi, otherwise known as ‘mycoviruses’, infect many of mycovirus replication. Disruption of RNAi within fungi can lead to excessive medically and commercially important fungi, but often do mycovirus replication, resulting in the dilapidation of fungal colonies. Several not cause obvious signs of disease. mycoviruses are known to interfere with fungal RNAi to prevent the inhibition of their replication. In the absence of an ycoviruses may have evolved Mycoviruses: nice guys finish last active RNAi system, fungi have been Mycoviruses growing on medium. Paul Rowley to minimise their burden upon In contrast to viruses of plants, animals shown to leverage alternative pathways Mfungi because their entire life and bacteria that were first described to limit mycovirus infection. For example, cycle occurs exclusively within their host around the beginning of the 19th within Saccharomyces cerevisiae the cell. Specifically, mycoviruses replicate century, mycoviruses eluded detection SKI genes target mycovirus RNAs for within fungi but are never released by scientists until the 1960s. This was degradation. Mycoviruses counter SKI from infected cells to the environment. mainly because most fungi infected genes by protecting their RNAs with Mycoviruses are transmitted to a new with mycoviruses do not exhibit any folded RNA structures, RNA modification host by cell division or cell-to-cell hallmarks of a ‘typical’ virus infection, or by stealing protective ‘caps’ from fusion. Consequently, if a mycovirus such as cell lysis or extracellular host RNAs. ‘Vegetative incompatibility’ were to cause severe disease, this disease transmission. Mycoviruses of is another striking example of how fungi would profoundly limit their own microscopic fungi were first discovered protect themselves from mycoviruses replication and spread, as their survival within antibiotic-producing strains of the by preventing cell-to-cell fusion between is inescapably linked to the success of Penicillium genus. These mycoviruses unrelated fungal species. This often their host. The apparent benign nature were only identified because their creates a line of demarcation between of mycoviruses may potentially explain double-stranded RNA genomes two incompatible fungi, usually due their widespread distribution throughout elicited an immune reaction in animals to cell death, blocking mycovirus fungi. However, fungi have not ‘rolled experimentally injected with extracts transmission. out the welcome mat’, as they mount from infected Penicillium species. From an evolutionary standpoint, many potent antiviral defences to limit Similarly, ‘killer fungi’, that produce competing virus–host interactions are mycovirus replication and spread. antifungal toxins, were described well known to select for the accumulation of Similarly, mycoviruses can subvert before the characterisation of the mutations that benefit either the host or fungal antiviral defences through a mycoviruses that are responsible for the virus. For example, if a mycovirus variety of fascinating mechanisms. The toxin production. were to steal a fungal protein to aid in study of mycoviruses offers many unique its replication, evolution would select scientific and commercial opportunities, Intracellular biological warfare for mutations within the fungal protein including the use of mycoviruses and Persistent virus infection requires that that would prevent its acquisition by their toxins to control pathogenic fungi, a virus replicates efficiently and spreads the mycovirus. Faced with an altered and as a model system to study the within a host population. Fungi encode fungal protein, compensatory mutations fundamental principles of virus–host a variety of antiviral mechanisms that may arise within the mycovirus that interactions. target mycoviruses to disrupt these again allows the hijack of the fungal

Microbiology Today Feb 16 | www.microbiologysociety.org 27

The broader application “ of mycovirus-based management of pathogenic fungi is worthy of further protein. This back-and-forth antagonistic the Totiviridae family of mycoviruses evolutionary cycle can be thought of for their stable maintenance. Satellite research, as there are many as a biological arms race, which leads RNAs ‘steal’ proteins that are produced to signatures of evolution that can be by totiviruses and use them for their examples of mycovirus- detected by statistical methods. There is own replication. Alone, totiviruses have dependent hypovirulence some evidence of arms race dynamics a minimal impact upon S. cerevisiae, but occurring within fungi; however, their the additional presence of satellite RNAs in pathogenic fungi of relevance to mycovirus infection remains provides an important example of a commercial fruits, tubers to be investigated. beneficial virus system. Viral killer toxins have been and cereals. Killer satellites described within many fungi, but there “ The budding yeast S. cerevisiae is are also examples of killer toxins an important producer of fermented produced from double-stranded DNA of killer fungi as biocontrol agents in foodstuffs and is chronically infected linear plasmids and the genomes of agriculture. with several different types of some fungi. Killer toxins can have a very mycoviruses. As a result of infection broad host range and kill important Mycoviruses as an antifungal by mycoviruses, ‘killer’ Saccharomyces human and plant pathogens, but the biocontrol yeasts secrete protein toxins that kill commercial use of these toxins is There are a considerable number of competing fungi. In the laboratory, often limited due to low environmental agricultural diseases that are caused killer strains cultured on solid growth stability, narrow host range and potential by fungal invasion of economically media produce dramatic clear zones toxic side effects. However, there has important plants. For example, chestnut free of other yeasts. These antifungal been some success in the production of blight is a canker-producing disease of toxins are produced by satellite double- novel antifungal antibodies and peptides Castanea species of chestnut, caused stranded RNAs that are dependent on derived from killer toxins and the use by the fungus Cryphonectria parasitica. The fungus was introduced into the USA from Asia in the 19th century, ultimately leading to the loss of an estimated half a billion chestnut trees, forever changing the woodland landscapes of North America. Microbiological analysis t grow h in f hi of recovering American chestnut trees o b e it i n o identified strains of Cryphonectria o n Z parasitica that were hypovirulent (less able to cause disease). Hypovirulence was found to correlate with the presence Killer yeast of a mycovirus of the family Hypoviridae. Efforts to control chestnut blight have used hypovirulent Cryphonectria parasitica to transmit mycovirus to pathogenic Cryphonectria parasitica. There has been mixed success of this

Non-killer yeast approach, as therapeutic outcomes appear to be dependent on factors such as the method of treatment application Circular colonies of killer S. cerevisiae producing a viral killer toxin that prevents the growth of a competing and the vegetative incompatibility of yeast strain. Paul Rowley hypovirulent Cryphonectria parasitica. The

28 Microbiology Today Feb 16 | www.microbiologysociety.org development of transgenic hypovirulent Cryphonectria parasitica to improve mycovirus transmission is an area of active research. The broader application of mycovirus-based management of pathogenic fungi is worthy of further research, as there are many examples of mycovirus-dependent hypovirulence in pathogenic fungi of commercial fruits, tubers and cereals. However, mycovirus infection can result in fungal hypervirulence (more able to cause disease), and so a comprehensive understanding of host–virus interactions would avoid potential undesirable outcomes of therapeutic mycovirus infection and increase the utility of current therapies. There are about 100,000 known fungal species (with an estimated 0.8–5.1 million species in total), but only about 250 mycoviruses have been so far discovered. With the current renewed focus on the development of novel antimicrobial compounds, the untapped diversity of mycoviruses could potentially improve our understanding of the evolution, mechanism and utility of mycovirus-based strategies focused against pathogenic fungi.

Paul A. Rowley Department of Biological Sciences, University of Idaho, Moscow, ID 83844-3051, USA [email protected] @DrPaulARowley

Further reading Ghabrial, S. (2013). Mycoviruses. Advances in Virus Research 86. Xie, J. & Jiang, D. (2014). New insights into mycoviruses and exploration for the biological control of crop fungal diseases. Annu Rev The structure of the L-A totivirus capsid from S. cerevisiae, which contains the viral double stranded RNA Phytopathol 52, 45–68. genome. Paul Rowley

Microbiology Today Feb 16 | www.microbiologysociety.org 29 Annual Conference Live at Lunch sessions Early Career Forum Launch Event 2016 Monday lunchtime, Hall 2F The Society is establishing a Forum for student and early career members of the Society. Early career members will be invited to join the Forum, which will be steered by an 21–24 March, ACC Liverpool Executive Committee elected from within the group. Join the President and Chair of the Professional Development Committee in a lunchtime session to find out more about #microbio16 the roles that will be up for election during 2016. An Audience With… The programme for this year’s Annual Tuesday lunchtime, Hall 2F Join Benjamin Thompson, Head of Communications, for Conference will be even bigger than before. an informal Q and A with our Prize Medal winner Professor With the conference attracting more speakers, Philippe Sansonetti. This will be an opportunity to find more about how Philippe discovered microbiology, a bit exhibitors and delegates, it is an event not to be about his background, his first hand hints and tips on how he developed his career, his breakthrough research, and missed! some of his highlights and challenges thus far. In addition to the full scientific programme, Big Data or Bust Tuesday lunchtime, Hall 2N there will also be the following activities. This one-hour lunchtime session is intended to stimulate discussion and raise awareness around this timely subject of data sharing and integration in the context Pre-Conference of pathogen genomics. During the hour there will be an interactive panel and audience discussion chaired by the Networking Workshop PHG Foundation. It will help inform the value of effective Sunday, 18:00–20:00, Hall 2N and responsible data sharing, and the challenges to data sharing and integration. On Sunday evening we will be holding our popular pre- Conference workshop. This is aimed at undergraduates, International Committee postgraduates and postdocs who are new to conferences or on Taxonomy of Viruses who want some tips on making new connections. The workshop Wednesday lunchtime, Hall 2F includes activities to hone your networking skills and enhance Join the International Committee on Taxonomy of your conference experience, as well as providing a chance to Viruses as they host a live debate on virus speciation and meet fellow delegates in advance of the Conference. phylogeny. The debate will be chaired by Ursula Gompels, The event requires pre-booking during conference registration – who will ask the panel challenging questions and there the ticket price is £12.00 per person and includes dinner. We will be a live vote. It will be followed by a networking hope to see you there! session.

30 Microbiology Today Feb 16 | www.microbiologysociety.org Follow the Society on Twitter to keep up-to-date: Liverpool waterfront. ACC @MicrobioSoc

Small World Initiative (SWI) Project Monday all day, Hall 2F Prize Lecture Winners The Small World Initiative is being supported in the UK and Ireland by the Microbiology Main Plenary Hall 1A Society and will give the general public, students and educators in the UK and Ireland Peter Wildy Prize Lecture the opportunity to work with scientists as part of a global initiative to discover new antibiotics from soil bacteria. It has initially run in undergraduate courses at six Professor Wendy Barclay universities and in eight school partnerships. A series of ‘pop-up’ events is giving the Monday, 18:10 public the opportunity to submit their soil samples and track the analysis process. If Microbiology Society Prize you would like to run the Initiative in your university, form a partnership with a school Medal Lecture or if you are interested in the Citizen Science project, come to this session. You can Professor Philippe Sansonetti also visit the Society’s stand at the Conference for information. Tuesday, 09:00 Meet the Speaker Monday–Wednesday, 19:30–20:30, Lower Gallery Fleming Prize Lecture Award Each evening we will be providing delegates and guests the opportunity to meet and greet some of the key speakers appearing at this year’s event. Located in the Dr David Grainger Lower Gallery with nibbles and comfy seating this event will provide you the perfect Tuesday, 18:10 opportunity to ask those pressing questions. Check our programme at the Conference Marjory Stephenson Prize Lecture for who will be making a guest appearance. Professor Steve Oliver Live Debate Tuesday, 19:15, Hall 2N Wednesday, 09:00 Why not join Jake Dunning and Stuart Nichol, who will be our hosts this year for Unilever Colworth Prize our lively debate? The debate will focus on the human face of Ebola and Ebola trials. Following this, we will provide some time and reflection to our members who have Professor Gurdyal Besra worked on the front line, looking at pictures and commending their contribution to Wednesday, 18:10 this research. Social Programme CPD credits Our Annual Conference has now MicroRoc Monday evening, Poster and Exhibition Space been accredited by the Royal Society of Biology (114 credits), Institute of Society members will be airing their musical talents on stage. Council members Biomedical Science (38 credits) and Nicola Stonehouse (Leeds – vocals) and Steve Diggle (Nottingham – bass) will be the Royal College of Pathologists (30 joined by ex-Council members Matt Hutchings (UEA – drums) and Mark Harris credits). Please ask the Professional (Leeds – guitar), together with Ville Friman (York – guitar), and some special guests. Development team at the Conference Science Showoff Wednesday evening, Poster and Exhibition Space for information or contact grants@ microbiologysociety.org You will have the chance to see a special gig from the highly recommended Science Showoff on Wednesday night. This is a chaotic science comedy cabaret featuring Steve Cross, and the gig will have a microbiology theme to showcase new ways to Online registration talk about and share the science of living things. Expect some guest stars from the Online registration is open until Conference, taking the stage in a completely new way. Monday 14 March. View the full Food can be purchased on site and a cash bar will be open until 22:00. We hope you programme and register today: www. can join us. microbiologysociety.org/conferences

Microbiology Today Feb 16 | www.microbiologysociety.org 31 Focused Meetings

Focused Meeting 2016: #Archaea5 Molecular Biology of Archaea 5 1–3 August 2016 s ller T. A London School of Hygiene and Tropical Medicine, London, UK

Scientific Organisers Thorsten Allers (University of Nottingham, UK) Malcolm White (University of St Andrews, UK)

Archaea were identified as a separate hypersaline lakes and deep sea vents. It is the fifth in the international group of organisms in the 1970s and This Focused Meeting is jointly conference series, Molecular Biology are the third domain of life, alongside hosted by the Microbiology Society and of Archaea. The conference will run over eukarya and bacteria. Archaea are the Genetics Society, with generous three days. On the first day of the meeting single-celled organisms that contain support from the BBSRC. The meeting there will be a BBSRC-sponsored workshop no nucleus or organelles and have supports the microbiology community on Genetic Manipulation of Archaea. some similarities with bacteria but are and its understanding of this domain of A wide range of prestigious, evolutionarily distinct. They survive life, highlighting how modern techniques, international speakers will be talking in some of the most extreme habitats including CRISPR, are aiding scientific at this meeting, including Tom Williams on Earth, including volcanic springs, understanding of this group of organisms. (Bristol University, UK), Julie Maupin-

Avian viruses have contributed Focused Meeting 2016: #Avian16 immensely to our understanding of not only virology but important aspects of Molecular Biology and Pathogenesis biology including cancer, immunology and cell biology. In recent years, the role of Avian Viruses of birds as sources of zoonotic viruses 27–29 September 2016, Charles Darwin House, London, UK (avian influenza, West Nile, Japanese encephalitis, the equine encephalitis Scientific Organisers Mike Skinner (Imperial College London, UK) viruses) has become apparent. With a Venugopal Nair (The Pirbright Institute, UK) plethora of viruses, and with frequent occurrence of emergence of novel pathogens and continuing diversity, the

vaccination strategies widely used by the

industry are being challenged. This timely

meeting focusing on avian viruses will

Mo nt ice lll o / iS to ck / T hi nk st o c k

32 Microbiology Today Feb 16 | www.microbiologysociety.org

Previous organisers Alain Kohl University of Glasgow, UK

s ller International Meeting on T. A

Arboviruses and their Vectors

The International Meeting on

Arboviruses and their Vectors (IMAV) 2015 was my first experience of running

Furlow (University of Florida , USA), a Focused Meeting. It turned out to be and Iain Duggin (University of Get a great occasion that really fulfilled the Technology Sydney, Australia). aims of bringing the community together “ “ involved and showcasing great science. The Key topics will include: experience and support of the Society • DNA, chromosomes and cell cycle The Society welcomes Focused team was hugely important in the smooth • RNA, CRISPR and viruses Meeting proposals throughout the organisation and running of the event • Molecular assemblies and protein year on any aspect of microbiology. – I and everyone else on the Organising modification The Scientific Conferences Committee are very grateful for all their • Genomes and evolution Committee meets twice a year to work and help along the way. review the proposals. If you have an bring together the international idea please complete the form online Nick Read scientific community to assess the and return to the Conference and University of Manchester, UK extent of the problem and help find Events Office by the next deadline, International Meeting on

solutions. 17 June 2016. The Invasive Fungus Focused Meetings offer

Topics will include: benefits to both delegates and Organising a Focused Meeting jointly • Molecular biology and genetics organisers in many ways, from between the Microbiology Society and the of avian virus replication networking to learning. We asked our British Mycological Society on the topic of • Tropism and host range 2015 session organisers to provide ‘The Invasive Fungus’ proved to be a joy! “ restriction us feedback on their experience. The exceptional administrative support • Pathogenesis of avian viruses “and interpersonal skills of the Society • Host antiviral responses and Submit your Focused team at every step along the way made

virus immunomodulation Meeting proposal. Visit: the meeting an outstanding experience

New and improved approaches • www.microbiologysociety.org/ and success for the organisers, speakers

to the control of avian viruses proposals and delegates.

Mo nt ice Registration and abstract lll o / iS to submission is open for both ck / T hi nk st meetings. Visit: o c k

www.microbiologysociety.org/

focusedmeetings

Microbiology Today Feb 16 | www.microbiologysociety.org 33

Editors and six Editors, increasing the international and diverse scope of JMM Case Reports the journal. The new additions to the Editorial Board will be influential to the advancement of the journal and the annual round up great efforts of existing Editors, who we thank dearly for their hard work. Elizabethkingia meningoseptica: an unusual cause for septicaemia, a Case Report in the ‘blood/heart and his year has seen an exciting working to pilot translated abstracts lymphatics’ subject category, has been development for JMM Case Reports, for JMM Case Reports. Of the journal, one of the most well-received papers of Tthe Microbiology Society’s first Dr Hall has said: “With high-quality the year. The paper was published last open access journal. We have seen the reviews and expedited publication, February and has gathered momentum journal move from strength to strength the Case Report can enjoy a revival, since 2015 (http://microb.io/1MIxeeS). and take on some pivotal changes, and return to its rightful place as the Thank you to everyone who has including publishing accepted papers source for the most up-to-date clinical had a hand in the growth of JMM Case within three days and Editorial Board isolates and research data on microbial Reports and we, the Society, hope that restructures. The journal also held its pathogenesis, evolution, epidemiology, the journal continues to develop and first board meeting at the Society Annual diagnostics, and of course case encourage the progress of medical Conference in Birmingham last year. management. It is particularly microbiology. Dr Robert Hall has joined JMM Case gratifying to be working with our Reports as a Co-Editor-in-Chief alongside professional society on a project Further reading Dr Johannes Kusters, who has been for the benefit of our international Swain, B., Rout, S., Otta, S. & Rakshit, A. influential in the creation of the Editorial microbiology community.” (2015). Elizabethkingia meningoseptica: an Board and progress of the journal. In The Editorial Board has also unusual cause for septicaemia. JMM Case Rep 2016, we will see both Editors-in-Chief expanded, taking on four new Executive doi:10.1099/jmmcr.0.000005

of Hull, UK. Professor Ratledge is one for Microbial Lipids was opened by Colin Ratledge of the foremost researchers in the field Professor Ratledge on 16 October 2015. of microbial oils that are produced It will develop new ideas as to how to Center for commercially as sources of various improve lipid production in a variety of Microbial Lipids polyunsaturated fatty acids. The Center micro-organisms.

new research centre for lipid research has been opened Aat Shandong University of Technology in Zibo City, Shandong Province, China. The centre has been named in honour of Society member Professor Colin Ratledge, Emeritus Professor of Biochemistry in the School of Biological, Biomedical and

Environmental Sciences at the University Ratledge C.

34 Microbiology Today Feb 16 | www.microbiologysociety.org Grants Where could a Microbiology Society grant take you? L. Sherry L.

uring 2015, Lee received three Dr Lee Sherry is a postdoctoral researcher at ENS de Lyon, different Society grants: a France. Lee previously undertook his PhD studying influenza DResearch Visit Grant, to support a trip to the Institute of Medical Virology, viruses, with Dr David Jackson at the University of St Andrews. University of Zurich, to work with Dr Jovan Pavlovic; a Society Conference Grant to present at our Annual the department in Zurich and received new chapter in my thesis. My visit also Conference 2015 in Birmingham; and a useful feedback that helped shape the broadened my search for potential jobs: Travel Grant to present at the American rest of my PhD project. I had previously only considered working Society for Virology (ASV) 34th Annual in English-speaking countries, but after Meeting in Ontario, Canada. We asked How was your experience of the trip I realised that I enjoyed working Lee how the grants have helped his presenting your research? in a different culture even if I didn’t professional development. I gave oral presentations at both speak the language. Now, here I am: the Microbiology Society and ASV working in Lyon, learning French as I go. What did you do during your conferences. It was a little nerve- research visit? wracking to begin with but I quickly Any advice for PhD students looking to We wanted to characterise the impact eased into the talks; by the end I was enhance their career prospects? of specific mutations in our protein almost enjoying myself! The talks were My main advice is to take advantage of of interest, MxA, using biochemical well received, and I was asked some any grants that are on offer. If there is an analysis of purified protein. The Pavlovic interesting questions, which were experiment that you would like to do but group were welcoming, making it followed up during the breaks. The talks is not possible at your institute, check very easy to settle in. To learn protein were great for networking and getting your eligibility for a Research Visit Grant. purification, I shadowed one of Jovan’s other perspectives on our work. It is a great opportunity to learn a new students, Patricia, who is an expert in technique, start a collaboration and even MxA purification, having purified many How did your experience of travelling, embrace a different culture. mutants throughout her PhD. collaborating and presenting help your I arrived in Zurich with my plasmids, career? To find out more about our grants, see ready to express the mutants. However, The conferences were both helpful for www.microbiologysociety.org/grants we didn’t get great expression. As learning how to succinctly disseminate a result we changed the plan and I my ideas in a short oral presentation; was only able to express and purify I can explain my work much more Maria Fernandes the protein – this was still a valuable clearly now. The research visit had a Professional Development Officer technique that I was able to take back to big impact on my PhD project as the [email protected] the lab. I presented some of my work to feedback received led to a completely

Microbiology Today Feb 16 | www.microbiologysociety.org 35 Schoolzone Fungi in schools: a neglected potential

Ten years ago, Moore et al. (2005) concluded that the most likely answer to the question “how much are your children taught about fungi in schools?” was “very little or nothing at all”. They remarked that the word ‘fungus’ did not appear in the then current National Curriculum for England Programme of Study for Science, and although fungi tended to be treated reasonably in the specifications for the GCSE Biology examinations, the references were largely along with bacteria as decomposers without reference to the basic distinction between the two groups.

he situation is a little better quality of responses to the MiSAC Annual Education, Quekett Microscopical Society, today but a feeling of missed Competition when a fungal topic is SfAM and Scottish Schools Education Topportunities to learn about a featured. Research Centre. group that is of fundamental importance The competition receives additional to so much of everyday life remains The MiSAC Annual Competition special sponsorship for prize money and among the sadly dwindling numbers of The annual competition is one of the administrative costs, usually from one professional mycologists as well as by main activities of MiSAC, an organisation of the annual sponsors. There are two concerned observers. founded in 1969 following a joint entry groups, Key Stage 3 and Key Stage Much effort has been made by initiative by the Society for General 4 (equivalent to ages 11–14 and 14–16, the British Mycological Society (BMS) Microbiology (now the Microbiology respectively), which attract entries from in attempts to remedy the situation Society) and the Society for Applied throughout the UK and often some from by lobbying educational advisers to Bacteriology (now the Society for Applied Ireland and British schools in Europe. examination boards and producing Microbiology, SfAM). The other main Each year’s topic is linked to the National a range of classroom resources and activities are developing information Curriculum but the requirements are materials, e.g. Fungi 4 Schools (see resources and practical activities, giving framed to encourage students to explore http://microb.io/1Oy1bg8). In addition, talks and workshops, providing advice beyond its boundaries. The topics range BMS is a sponsor of the Microbiology in through a helpline, and serving as a widely over areas such as environmental Schools Advisory Committee (MiSAC) recognised authority on health and issues, health care, food production and whose activities show that whatever the safety (see www.misac.org.uk/about. food safety. Other topics have involved position of formal mycology education, html). MiSAC is a voluntary organisation producing a social media profile for a there is an untapped interest and funded by annual sponsorship from microbe and a requirement to use a enthusiasm for the subject in schools. BMS, CLEAPSS, Microbiology Society, microscope. The requirements specify a The evidence lies in the high level and National Centre for Biotechnology particular format, e.g. information leaflet,

36 Microbiology Today Feb 16 | www.microbiologysociety.org poster or news article, and target group, Above: from left to right e.g. classmates or the general public KS3 winners (1st, 2nd, (see www.misac.org.uk/competition. 3rd) and KS4 winners (1st, html). The requirement for 2016, the 2nd, 3rd). 28th competition and funded by SfAM, is to produce a news story for an internet Right: Thai schools news media site on ‘How microbes work competition winners (from for us’. left to right 1st, 2nd, 3rd).

Fungal topics in the UK the opportunity to discuss the teaching mycoprotein, the normal gut flora and BMS has funded the following MiSAC of microbiology in schools in Thailand, probiotics, although oriental foods were competition topics: ‘Fungi: friends and Malaysia, South Korea, Taiwan and China. not entirely neglected. foes’; ‘I’ve got you under my skin: Fungal This involved meetings with government The competitions were arranged infections of the human body’; ‘Fungi in officials, presenting UK teaching to coincide with international mycology your shopping trolley’; ‘Medicines from materials including those produced conferences held in Bangkok (10th fungi’; ‘Helpful and harmful fungi’; and by MiSAC and BMS to teachers and International Mycological Congress ‘Fearsome fungi’. It is encouraging to for teacher training, and co-producing in 2014) and in Khon Kaen (Mycology report that the number and quality of the a range of microbiology educational in Southeast Asia in 2015), and entries is always on a par with those on resources in some of those countries in attracted entries from all over Thailand. other aspects of microbiology. collaboration with educational institutes. Successful posters were displayed on, In view of the theme of this issue One particularly successful and winners participated in, the final day of Microbiology Today, it is appropriate approach was to introduce the concept of the conferences where they explained, to provide a flavour of the student of competitions for students by using in English, their choice of approach for experience by reference to ‘Fearsome the well-established MiSAC model. This the poster and were presented with fungi’, the topic in 2014. The objective work bore fruit first of all in Thailand in money awards and certificates by the was to produce a poster to inform the form of competitions on fungal topics President of BMS. classmates about one fungus of choice in for students aged 14–16 in 2014 and 16+ The success of the two competitions a specific event of historical importance in 2015. They were jointly sponsored by has been such that IPST intends to make or more recently newsworthy. As usual, the Institute for the Promotion of Science it an annual event for Thai schools. a list of possibilities was provided for and Technology Teaching (IPST, part of Furthermore, a similar competition, guidance. Those who chose an historical the Thai Ministry of Education), BMS and supported by BMS and MiSAC, is event referred mainly to the Irish potato MiSAC, of which the latter two provided currently being organised in China in famine (expressly allowed for purposes financial support and organisational 2016 to coincide with the International of the competition), the Witches of Salem expertise, respectively. Mycology Meeting in Changchun, and the First World War. Those who The purpose of the competitions Manchuria. focused on a more recent or present day was to produce public information problem referred mostly to poisonous posters on ‘Helpful and harmful fungi’ Margaret Whalley and John Grainger and psychedelic mushrooms, diseases of (2014) and ‘Fungi and healthy living’ Microbiology in Schools Advisory the skin and lungs, and losses affecting (2015). The latter topic was particularly Committee (MiSAC) bees, frogs, crops and trees. interesting to us in the UK in that most [email protected] entries focused on the Asian tradition Fungal topics in Southeast Asia of using fungi such as shiitake or Further reading While visiting Southeast Asia over Ganoderma lucidum for enhancing Moore D. & others (2005). Mycologist 19, several years to conduct mycology health whereas responses to a similar 152–158. research, one of us (M.W.) has taken theme in the UK gave most attention to

Microbiology Today Feb 16 | www.microbiologysociety.org 37 Outreach Microbiology comes to Harvey Nichols

Professor Jo Verran launched a series of food microbiology events as part of Manchester Science Festival.

‘Menus Made By Microbes’ was the who founded the hugely successful first in a series of events designed to MetMUnch (www.metmunch.com give micro-organisms a more positive /@MetMUnch), student-led social image by raising awareness of their value enterprise at Manchester Metropolitan in food production, food preservation University, and chef Richard Fox and nutrition. The event was inspired (www.richardfoxcooks.co.uk), award- partly by previous events hosted by the winning writer, cook book author and Microbiology Society and the Society for chef presenter, also known as the ‘beer Applied Microbiology at the Cheltenham chef’. The team designed a wonderful Science Festival – the former hosting a high-class menu that presented a sit-down menu, the latter focusing on fantastic range of food. Richard worked cheese and wine. with the chef at Harvey Nichols on the Over the next 12 months, design and delivery of the different microbiologists at Manchester courses. The resultant five-course menu Metropolitan University will be hosting utilised a range of foods that owed their events that encourage different audiences nature, flavour, smell, nutritional value to enjoy some wonderful and diverse and/or texture to micro-organisms. foods whose origins or processing we Wines were donated by Alliance des Crus owe to micro-organisms. What better Bourgeois du Medoc, and were served at way to learn than through eating! table along with the food by the waiting The first of these events took place staff. during Manchester Science Festival, Each table of 10–12 was hosted by in the Harvey Nichols restaurant in the a microbiologist, a nutritionist, or the Manchester store, and was directed at an chef. Almost 50 members of the public adult, ‘gastronaut’ audience. Preliminary attended the evening, including members planning involved microbiologist of the development team for the City of Professor Joanna Verran working with Science programme. The evening began All event photos Natasha Hall-McKenna nutritionist colleague Haleh Moravej, with a drinks reception and vertical

38 Microbiology Today Feb 16 | www.microbiologysociety.org canapés before guests went to their Feedback was plentiful and positive. The Menu tables. Jo and Richard turned out to be The quality of the food and the service an excellent comedy duo, providing an was complimented, as was the expert but Drinks Reception – 7pm entertaining discussion/demonstration informal and entertaining ‘double act’ of Libby Riley’s ginger beer on arrival* addressing many aspects of the microbiologist and chef. The nature and Sparkling lemonade as non-alcoholic microbiology that had contributed to the content of discussion at table varied, but alternative menu and accidentally highlighting some always included some microbiology. of the misconceptions around different Our next event will take place in Canapés types of micro-organisms. Subsequently, March, during British Science Week, Welsh rarebit, sourdough crostini additional courses and wine were served and will focus on a ‘Ploughman’s tapenade, sour cream polenta at table, and diners were free to discuss lunch’ – bread, pickles and cheese Bar the menu, the microbiology – or whatever alongside some beer. In July, during the Including a special microbe-inspired they wished – with one another, and with celebrations for Manchester European cocktail from Harvey Nichols: their hosts. All diners were invited to City of Science, we will host a World Black truffle magic: a wondrous mix of keep their menu cards, provide feedback, Family Picnic, encouraging picnickers to whisky, coffee, chocolate and truffle and take with them a gifted ‘Mind your bring as many diverse fermented foods perfume Microbes’ fridge magnet. as possible to the party. Our final event, (non-alcoholic version also available) in September, will be a street food event, focusing particularly on Asian-style, stir- Call for dinner – 7.45pm fry type foods. Introduction and demonstration Acknowledgements Dinner – 8.30 We would like to thank the Microbiology Complimentary wines at table Society and the Society for Applied (one glass per person) Microbiology for sponsorship of the event. Kindly provided by Alliance des Crus Bourgeois du Médoc Joanna Verran Appetiser Faculty of Science and Engineering, Prosciutto platter, apple and Manchester Metropolitan University, sultana sauerkraut Chester Street, Manchester M1 5GD, UK [email protected] Starters Please visit our website for more Warm salad of deep-fried Roquefort information: and smoked tofu, Sauternes poached pears www.menusmadebymicrobes.com

Mains Truffled mushroom risotto, rosemary and beer flatbread

Dessert Chocolate tart, framboise beer sauce Served with Kriek beer Tea/coffee and chocolate petit fours

*Recipe from Microbes on the Menu, published by the Microbiology Society

Microbiology Today Feb 16 | www.microbiologysociety.org 39 Membership Q&A

In this issue, we’re pleased to introduce Dorina Timofte. D. Timofte D.

Where are you currently based? in resistance seen in clinical isolates, findings, we hope to raise awareness Since 2009 I have been an academic at but also we need to make sure that the of the danger posed by the spread of the Liverpool School of Veterinary Science information that is sent out to clinicians carbapenemase-producing organisms in and I am based at the Leahurst campus, is accurate, tailored to each case and the absence of coordinated surveillance at a green and leafy part of the Wirral does not encourage further development hospital and national level in Romania. peninsula. of resistance. As a microbiologist and a parent, I do worry about the prospect of Tell us about your education to date What is your area of specialism? a world in which penicillin would not be I completed my formal school and Veterinary clinical microbiology. I lead effective anymore for treating a child’s university education in Romania. I gained the Microbiology Diagnostic Laboratory streptococcal infection. a Doctor of Veterinary Medicine from in the Liverpool School of Veterinary I feel that it is also important that our the Faculty of Veterinary Science at Iași Science, which is a very busy, but vibrant experience is shared internationally and Agricultural University in 1991. The anti- environment. The clinical material I found the International Development communist revolution happened while I received frequently leads to research Fund (IDF) scheme of the Microbiology was in my final years at university and projects and is also used for teaching Society an excellent vehicle to share this coincided with universities opening veterinary students about the all- my experiences and to contribute to their doors to younger staff; therefore, important relationship between clinics the training of other microbiologists in I did not hesitate when a position of and the laboratory findings. Our activities the area. I was awarded an IDF grant in teaching assistant was available in the are very similar to those of a human 2012, which supported the organisation microbiology department of the faculty clinical microbiology laboratory, where, of a workshop in Romania, aimed at where I graduated. In 1992 I embarked every day, there are clinicians waiting for transferring knowledge and technology on a six-year PhD programme, which was quick, quality results and a patient that to local diagnostic laboratories on available on a part-time basis allowing needs the best possible health care. laboratory detection of extended me to continue my academic career at And more specifically? spectrum beta-lactamases (ESBL), the same time. The quality of our diagnostic product meticillin-resistant Staphylococcus aureus and our training is key for current and (MRSA) and other resistance phenotypes. Where did your interest in future therapeutic management of Both human and veterinary diagnostic microbiology come from? animal patients with clinical infections. microbiologists attended and it was the I always enjoyed biology in general but Furthermore, the rise of antimicrobial first time in Romania when human and decided to take a degree in the more resistance, which we find in farm and veterinary microbiologists had met to complex subject of veterinary science. companion animals, led me to develop discuss the problem of antimicrobial Microbiology was the subject that I most an interest in understanding the role that resistance. Given the success of this enjoyed studying and I was fortunate to be particularly companion animals may play first workshop, I re-applied to the IDF offered the position of teaching assistant as a reservoir of resistance genes, as well scheme in 2014, this time proposing in microbiology at Iași. as the bilateral interspecies transfer that work with human microbiologists can occur between humans and animals. in Romania to tackle the emerging What are the professional challenges From this point of view, the diagnostic problem of carbapenemase-producing that present themselves and how do you lab is very well placed for surveillance Gram-negative organisms. In this try to overcome them? of the trends in antimicrobial resistance. project, the IDF funds have supported a In my day-to-day job, the biggest We play a key role in understanding the pilot project for the implementation of challenge is getting the right balance cloudy picture of antibiotic resistance detection of carbapenemase-producing between teaching veterinary students, development, both as a receiver and Enterobacteriaceae and non-fermentative pursuing my research interests, deliverer of information. As such, we bacteria in two Romanian hospitals. developing new diagnostic assays and need to capture the waves and trends The project is ongoing and through its getting involved in all the clinical cases

40 Microbiology Today Feb 16 | www.microbiologysociety.org that pass through our laboratory. I am Yorkshire philosophy to ‘always get the luxury item – my espresso coffee also a strong believer that family should things done’, is now embedded in my pot; it helps me function in the morning. always come first, and there are already work ethic. Stuart and I met via an EU too many things to balance and I am not teaching exchange programme, and got Tell us one thing that your work sure if I do meet that particular challenge. married soon after that; therefore, we colleagues won’t know about you! nominate ourselves as the ideal example I could say I used to be a painter as I What is the best part about ‘doing of a successful European collaboration. also graduated from arts school, but science’? unfortunately I have not touched any There are a lot of things, I enjoy the What do you do to relax? brushes since being in my current job. ever-changing scenes and that two days Whenever I get the chance I try to follow are never the same. I guess a research my passion for gardening. Working in If you weren’t a scientist, what project can be a little bit like a piece of art, the garden has the power to take away would you be? where it is all in your mind, you just have all my work thoughts and worries. Being Either a painter or a landscape gardener. to give it shape and make it relevant and between my flowers is therapeutic and It would be difficult to decide which one interesting for other people as well. de-stressing, but I can’t explain how it of the two. works. Who is your role model? If you would like to be featured in In life, Audrey Hepburn, especially for What one record and luxury item this section or know someone who the charity work that she did as a UNICEF would you take to a desert island? may, contact Paul Easton, Head of ambassador. In science, probably my The record would be Romanian choral Membership Services, at husband, Professor Stuart Carter, whose music by the Madrigal Ensemble and [email protected]

Microbiology Today Feb 16 | www.microbiologysociety.org 41 We are the Champions

The Champions scheme was launched at our Annual Conference in 2014, and our Champions have been busy since then, spreading the microbiological word far and wide. Their efforts have been diverse, reflecting their own wide range of interests and expertise.

n the past 18 months, around of 70 delegates attended including In terms of wider more 20 events have been held in the representatives from Australia, Japan, mainstream engagement, it’s hard IUK, Ireland and other countries, Russia, China, Taiwan, India, Pakistan, to go past food and drink as the including Turkey. We estimate more Qatar, Iran, Iraq, Turkey, Spain, France, vehicles through which to gain an than 1,000 people have been involved Denmark, UK, USA and Mexico. Agah’s audience’s attention. This was proven in a Champions-related event and have efforts on behalf of our Society and on two separate occasions during been introduced to the Society as a the other partners involved produced the year. Our Champion in Dundee, result. Here’s just a small taste of a symposium of world-class standing. Marilia Costa, hosted a pub quiz with a what they’ve been up to. “Symposia like this are a very good microbiology-themed suite of questions Our Champion based in Turkey, chance for our regional postgraduate and succeeded in delivering a very Agah Ince, helped coordinate the students to come together to hear successful night to colleagues and first symposium of Blastocystis the most up-to-date information friends. “People love pub quizzes,” at the Gazi University Faculty of and research methods on microbial said Marilia, “and I thought, why Medicine, Ankara, in May 2015. A total genomics” said Agah. not a microbiology one? I organised

Blastocystis conference Ankara Turkey. Agah Ince JAM talk Birmingham. Amanda Rossiter

42 Microbiology Today Feb 16 | www.microbiologysociety.org the event to be open to everyone but Arikana Massiah (left) and Ben mainly undergraduate and PhD students Johns (right) at FIS. Microbiology attended. It was exciting to see them Society thinking, talking and discussing the questions. It was a fun night and I am sure people learned something new about the micro world.” On a similar theme, Tadhg O’Croinin, our Dublin-based Champion, hosted a two-day event introducing Brewing event Dublin. UCD the wider public to the mysteries of Science brewing. “This workshop was extremely successful in that it helped students can meet up at Conference; and it raises at different stages in their career, which not only to understand the science the awareness of the Society too. was great for networking. I would most behind the brewing process but also Over the past months, we have certainly do this again.” the critical role that microbiology plays looked closely at Champions to see how Ben thoroughly enjoyed his in this important industry and the we can make the initiative even more experience too. “There were some broader biotechnology sector.” Both relevant and attractive for members. As fantastic lectures given on a wide variety events struck a chord with audiences a result we are changing the focus of it of topical subjects, a good selection relatively new to microbiology and, somewhat. of stalls from different exhibitors and judging by the feedback, both will Champions will in future be offered some useful networking opportunities have a very definite place in future more opportunities to become involved in the hall during poster sessions. As a programmes. in Society-led initiatives as well as those Society Champion I found attending this We were delighted to see a new of their own. For example, we intend to conference invaluable.” initiative coming from a Birmingham- offer Champions more roles at our own Further opportunities will be based Champion, Amanda Rossiter. events, which may be developmental presented to Champions in the coming Amanda and some of her colleagues are or call more on their existing skills months. If the Champions initiative running a series of ‘JAM Talks’ (Junior and expertise at different levels. This is something that sounds of interest Award in Microbiology Talks). This is a way Champions can use their Society to you, why not get in touch? We are series of talks by PhD students, which experiences to build their own CVs always looking for more members to will be ‘judged’ by visiting peers from and networks to develop their careers, get more closely involved in our work. other universities, with a prize awarded while at the same time helping build If you would like to find out more about to the best presentation at the end of the Society. The first practical example the Champions and how to become one, the series. It’s a brilliant idea. Students of this saw two Champions, Arikana please contact me. get involvement in an awards scheme Massiah and Ben Johns, attend the and can use this to enhance their CV; 2015 Federation of Infection Societies Paul Easton visiting judges can take the idea back to (FIS) Conference in Glasgow as Society Head of Membership Services implement in their own universities; it representatives. As Arikana said, “I [email protected] grows an informal network of students got to meet scientists from different +44(0)20 7685 2680 and colleagues across universities who backgrounds and specialities who are

Microbiology Today Feb 16 | www.microbiologysociety.org 43 Honorary Archivist

The Microbiology Society has a long-standing history and a role has been created to ensure the knowledge in the Society archives is maintained. The role has been taken up by Gilbert Shama. We asked him about his background and what intriguing items he has found in the archives during the initial stages of his research.

Where are you currently based? Microbial Physiology from Imperial I am currently working in the College, London. Department of Chemical Engineering at Loughborough University. Where did your interest in microbiology come from? Khayat P. What is your area of specialism? I didn’t study biology at school, but What is the most interesting item I am involved in a number of became introduced to microbiology you have found in the archive so far? activities; they mainly are concerned through biochemical engineering which I was examining a photograph at the with eradicating micro-organisms I studied as part of my first degree and, Society offices of what I believe is an from various media and environments. I I suppose one could say, became unpublished photograph taken at the started quite a few years ago with hooked! International Congress for Microbiology in UV light as a means of sterilising 1936. I was scanning the sea of faces of liquids, and then extended my research What will your role as the attendees seated round tables at what to include the surfaces of solids Honorary Archivist involve? must have been the Congress Dinner including foods. More recently I have The Society will be celebrating the 75th when the face of Alexander Fleming been investigating the elicitation of year of its foundation in the year 2020 jumped out at me – it was as though I had hormetic responses in fresh produce and the post was created principally with encountered an old friend! as a means of preventing food wastage this anniversary in mind. I am looking through fungal spoilage. I’m also forward to working with the staff of the What are you most looking working closely with electrical engineers Society as they prepare for 2020, and forward to finding in the archives? on the application of atmospheric also in meeting with Society members What excites me most about going pressure gas plasmas for similar and hearing their views as to how the through archives is simply not knowing applications to those described above occasion should be marked. what one will come across – coming in relation to UV. face to face with the unexpected. What made you apply for the Tell us about your education role of Honorary Archivist? What most excites you to date The prospects for communicating about the history of science? I attended Kilburn Grammar School in the history of the Society and the I would say uncovering previously London. My first degree was in Chemical achievements of its members to both unknown facts but also making novel Engineering from UMIST. I then went on the current and future generations of connections between the past and the to take an MSc in Biological Engineering microbiologists as well as to the public present. from Birmingham. My PhD was in at large.

44 Microbiology Today Feb 16 | www.microbiologysociety.org Caenorhabditis elegans. National Institutes of Health

s we start to peer blinking using bacteria to mine asteroids and into the light of a new spring Martian rock (no, really). Ahere in the UK, it’s time to have In other Martian news, I spoke a little look back at some of the content Best to the astrobiologist Dr Lewis we posted on our blog at the end of Dartnell about the recent discovery 2015. of liquid water on the Red Planet, Last year, Society member of the and what this might mean for the Dr Lucy Thorne visited the Uganda field of microbiology. In the same Virus Research Institute in Entebbe episode, Anand spoke to Dr Kevin with support from one of our Research Newsham about the impact of Visit Grants. Lucy kindly videoed blog climate change on soil fungi her trip when she went to the (http://microb.io/1H79P2n). laboratory of Professor Alison Elliott star-like formations. This post contains Lastly in this roundup, it’s worth to find out how common intestinal an amazing GIF that’s well worth your noting some of the places where new viruses are in Ugandan children time. microbes have been discovered. Over (http://microb.io/1M6PVWI). The last of our 2015 Focused the past few months, they’ve been At the time of writing, the Meetings was about the Industrial isolated from such diverse locations new Star Wars film is yet to be released Applications of Metal–Microbe as sea urchins in the Sea of Japan (hopefully it’ll be good); not such a Interactions. Two blog posts came from (http://microb.io/1Po3GaO), long time ago, we had a post entitled research presented at the meeting: one, the Russian wheat aphid Deadlier than Darth: Death by worm-star written by Anand Jagatia, about how (http://microb.io/1WhyLk7) and the (http://microb.io/1Z6Iwkb), which microbes may help in the detection of faeces of penguins in the Antarctic. details work by Society member arsenic in drinking water in Bangladesh Dr Laura Clark on the discovery of a (http://microb.io/1MuKg0Y), the other Benjamin Thompson new species of bacteria that causes about research from the University of Head of Communications Caenorhabditis elegans worms to stick Edinburgh (http://microb.io/1kmMhSG) [email protected] together by their tail spikes in lethal that is investigating the possibility of

Microbiology Today Feb 16 | www.microbiologysociety.org 45 Reviews

Human Fungal Pathogens delineated sections (e.g. role of fungi in disease), making it easier to find the infectious disease, syndromes associated information required. Edited by A. Casadevall, A. P. Mitchell, with fungal infection, mechanisms of J. Berman, K. J. Kwon-Chung, J. R. Perfect disease, laboratory diagnosis, antifungal Christopher Ring and J. Heitman treatment and drug susceptibility testing, Middlesex University Cold Spring Harbor (2015) new development in the study of fungal US$135.00 ISBN 978-1621820758 Bacteria–Plant Interactions: the most recent citations are from There are some very good texts on 2013. The second is that there are not different types of infectious agents Advanced Research and Future focused chapters on pathogens from but there is a definite need for a good Trends the Xanthomonas, Ralstonia, Xylella, textbook devoted to fungal pathogens. Edited by J. Murillo, B. A. Vinatzer, Agrobacterium or Pectobacterium genera, all of which are among the most The book, as the title indicates, is about R. W. Jackson and D. L. Arnold the fungi that infect the human host. The economically important plant pathogens. Caister Academic Press (2015) focus is very much on the fungus (e.g. For example, there is no description classification, evolution and genetics), £159.00 ISBN 978-1910190005 of the xanthomonad Transcription- rather than the human disease, which Activator-Like Effectors (TALEs) and is fine if your interest is more in fungal A lot has been discovered recently in the how their internal repeats of amino-acid biology than the role they play in disease. area of bacterially made effectors that sequences define DNA recognition sites. I believe that the book would have can modify different aspects of plant Perhaps the absence of such chapters benefitted from an introductory chapter signalling. The opening chapter provides a reflects the intended perspective of putting fungi in context of other infectious useful integrative overview of evolutionary this book, but if that is the case, the agents in the role that they play in human relatedness and targets of several of absence of chapters on the associative or disease, and the expanding importance these effectors delivered to plants via symbiotic nitrogen-fixing bacteria, or the of fungi with increasing numbers of the Type III secretion systems of various rapidly developing areas of rhizosphere susceptible hosts due to HIV infection or bacterial plant pathogens. One of the best and phytoplane genomics is also a immunosuppressive medical procedures. models is Pseudomonas syringae, and so significant omission. If the book is aimed Also, I feel there should have been more inevitably, there is some overlap with the at generalists, then it is rather lacking in about the clinical syndromes associated chapter by Lindberg & Collmer, focusing schematic models in most chapters. If with fungi. There is a whole section on the transfer, evolution and mechanisms it is aimed at specialists, then it has the on treatment but relatively little on of loss and biological activities of problem of its citations already being diagnosis or drug susceptibility testing. effectors produced by P. syringae. The a couple of years out of date. Perhaps In terms of diagnostics, newer molecular chapters on (a) the fire blight pathogen I am reflecting on the impossibility of techniques are better covered than more Erwinia amylovora, (b) Acidovorax spp., (c) simultaneously having such a book be conventional methods still widely used Gram-positive bacterial pathogens and both up-to-date and comprehensive. in some laboratories. Chapters are not (d) human pathogens on plants, are all Balancing the costs of books such as this, numbered and there are no obvious good perspectives on these areas, well against the potential speed of publication delineations between groups of chapters referenced and would be a good starting and rapid availability of reviews via into different sections, although the point for people wanting an overview. Two web-based publications, perhaps my Contents page suggests that there are. chapters are related to biocontrol, and the reservations should be seen as more This doesn’t help with navigating around final chapter is a summary of the biology broadly questioning the viability of this the book when in search of information. of phages and how they may influence the genre of publication. There is a vast amount of interesting and populations of bacteria interacting with useful information, but in my opinion plants. Allan Downie the content could have been laid out in a As a reference work, this book John Innes Centre more logical fashion, with more clearly has two limitations. The first is that

46 Microbiology Today Feb 16 | www.microbiologysociety.org Comment

Low-cost whole genome Pathogen genomics into sequencing technology is practice: from promising catalysing a transformation research to real health in the way clinical and public health microbiologists and impact epidemiologists can manage the Sowmiya Moorthie and Leila Luheshi threat of infectious diseases. In comparison to existing

Least sensitive microbiological methods, raw Data 10 sequence genomic methods offer greater data generators 1 2 1 2 1 2 e.g. public e.g. hospital-linked e.g. specialist assembled health reference microbiology/ clinics 9 pathogen sensitivity and specificity, as laboratories virology genome 8 well as providing a description 7

public domain e.g. ENA public health authority – 6 of a wide range of clinically restricted access Data 5 Computational Computational infrastructure metadata storage/ 10 9 8 7 6 5 4 3 and epidemiologically relevant collation 4 3 characteristics of a pathogen, 2 including identity, virulence 1 Data determinants, drug resistance accessibility Most sensitive and relatedness to other e.g. researchers, e.g. authorised users (clinical commercial, public or public health consultants) pathogens.

be essential to realising the benefits The size of circles (not to scale) are indicative of the relative data storage burden (computational disc space) of genomics for infectious disease of the different subsets of data. Raw genomic data will consume the greatest disc space (therefore costing management; the most fundamental more to store than other data types) and so its longer term storage would be better suited in a consolidated components of this system being cross- repository for high-volume data storage. PHG Foundation organisational data integration, strategic n principle, genomics can be used to to accrue only when it is deployed at coordination and strong leadership improve the management of infectious scale, in an integrated health system- to manage the radical changes in Idisease by allowing more precise wide manner. As it is more or less microbiology service provision that will diagnosis, detection and tracking of impossible to pilot such an approach be required. antimicrobial resistance and outbreak without significant capital and resource Obtaining clinically useful control. However, in practice evidence investment, a ‘calculated risk’ may have information from pathogen genomes is demonstrating that genomics improves to be taken to commit to a genomic reliant on our ability to compare them patient care or population health, and future for microbiology well in advance to other genomic data and combine this is affordable when implemented in of all the necessary scientific evidence with relevant epidemiological or clinical ‘real world’ pathways within the NHS, being available. information. The success or failure of remains limited. Problematically, many A nationally coordinated system of genomics as a tool to improve infectious of the benefits of genomics are expected service development and delivery will disease management will depend

Microbiology Today Feb 16 | www.microbiologysociety.org 47 heavily, therefore, on the timely collation, integration and sharing of genomic and clinical/epidemiological metadata across the health system. These actions will also underpin the research and development needed to drive the expansion of the utility of genomics to a wider range of organisms and investigations than are currently feasible. Achieving this vision of genomics- enabled microbiology services that are continuously innovating and expanding in scope requires the development of

infrastructure to provide repositories Standarisation and Strategic coordination Repository function Collaboration function for data, knowledge and samples, along expertise function and development function with quality standards and data privacy system will look. The benefits of such some infectious diseases in the near safeguards to ensure their responsible a cooperative approach are that the future. However, realising this vision use. This is no easy task considering health system will be able to minimise necessitates overcoming current the large number of different groups duplication of effort, and share both technological limitations and improving involved in producing and using this data, resources and risks. our understanding of the clinical and from front-line clinical staff, genomics In addition to this ‘top down’ strategic epidemiological significance of genomic researchers and clinical scientists, collaboration, it will be equally important variation, with the concomitant adoption through to national agencies involved in to bolster ‘bottom up’ cooperation of this new knowledge by health services food safety or animal health. The task amongst ‘front-line’ professionals. By in a timely manner. We are convinced this is further complicated by the fact that sharing and developing knowledge, can be achieved if a prompt, concerted infectious diseases do not recognise expertise and best practice around effort is made to share data, knowledge borders, and so international cooperation genomics, they can accelerate delivery and expertise and if the strategic on these issues will also be essential. of the highest quality care to patients coordination and leadership needed to Although it may seem a daunting prospect, and improve the protection of the health deliver a whole system approach are acting now to develop these mechanisms of our population. This means providing provided by those tasked with protecting wherever possible, while many services opportunities and systems to gather the public’s health from infectious are in the relatively early stages of input from a wide range of professional diseases. development, will lead to future benefits groups, ranging from infectious disease as sequencing becomes more widespread physicians, medical microbiologists Sowmiya Moorthie and Leila Luheshi and the need for a coordinated approach and infection control nurses, to clinical PHG Foundation, 2 Worts Causeway, becomes ever more pressing. laboratory scientists and academic Cambridge CB1 8RN, UK Effective development of a national researchers, all of whom have a stake in [email protected] data management system to deliver the realising the effective development and benefits of pathogen genomics now and implementation of pathogen genomics Further reading in the future will not happen organically. services. PHG Foundation (2015). Pathogen Genomics Instead it will require strategic leadership From our extensive analysis of the Into Practice. www.phgfoundation.org/ and coordination. The various disciplines technology, health service, microbiology file/16849/. July 2015. and organisations involved must agree systems and extensive stakeholder PHG Foundation (2015). Infectious disease on and work towards a common vision consultation, we believe that genomics genomics project. www.phgfoundation. of how a future genomics-enhanced could, and indeed will be used as a org/project/id. Last accessed 7 December 2015. infectious disease management front-line tool in the management of

48 Microbiology Today Feb 16 | www.microbiologysociety.org

Bleed: 5 mm Supply as hi-res PDF Job no: 00530 no: Job PDF hi-res as Supply mm 5 Bleed: mm 210 x 297 Size:

Journal: Journal: Microbiology Today Microbiology Essential Generics: Chloramphenical Ad Chloramphenical Generics: Essential 04/12/2015 11:51 CHL25060 O65995 ALLIANCE: MOVIANTO: AAH: CHL600B PIP: 106-5796 CAPSULES

CHLORAMPHENICOL 1 2 3,4 Adverse events should be reported. Reporting forms be reported. Adverse events should can be found at www.mhra.gov.uk/ and information events should also be reported to yellowcard. Adverse Essential Generics on 01784 477167. irregular respiration and death within a few hours of the onset of irregular respiration and death within a few hours of the onset symptoms. Overdose: Stop chloramphenicol immediately if signs of adverse events oral develop. Treatment is mainly supportive. If an allergy develops, Baby antihistamines may be used. In severe overdosage e.g. Gray Resin Syndrome, reduce plasma levels of chloramphenicol rapidly. increase haemoperfusion (XAD-4) has been reported to substantially chloramphenicol clearance. Pack size and Price: 60 capsules £377.00 Legal Category: POM. Market Authorisation Number: PL17736/0075. Market Authorisation Holder: Chemidex Pharma Limited, 7 Egham UK. Business Village, Crabtree Road, Egham, Surrey TW20 8RB, Date of preparation: October 2014. for See Chloramphenicol Capsules Summary of Product Characteristics full prescribing information. References: 1. Martindale: The Complete Drug Reference. Chloramphenicol. [Online]. Available from: http://www.medicinescomplete.com [Accessed 17th September 2015]. 2. Fluit, A.C., Wielders, C.L.C., Verhoef, J., and Schmitz, F.J. Epidemiology and susceptibility of 3,051 Staphylococcus aureus isolates from 25 university hospitals participating in the European SENTRY Study. Journal of Clinical Microbiology. 2001; 39(10): 3727-3732. 3. Kelly, C., LaMont, T. Patient information: Antibiotic- cile). www.uptodate.com. 2011. associated diarrhea (Clostridium diffi 4. Bartlett J.G. et al. Antimicrobial agents implicated in Clostridium cile toxin-associated diarrhea of colitis. Johns Hopkins Med J. 1981; diffi 149(1): 6-9. 5. Feder. H, Chloramphenicol: What we have learned in the last decade. Southern Medical Journal. 1986; (79)9: 1129-34. 6. Weigel LM et al. High-level vancomycin-resistant Staphylococcus aureus (VRSA) lm. Antimicrobial Agents and associated with a polymicrobial biofi Chemotherapy. Published online ahead of print on 30th October 2006. http://aac.asm.org/cgi/reprint/AAC.00576-06v1.pdf. (Accessed on 17th September 2015). 7. Ensminger, P., Counter, F., Thomas, L., Lebbehuse, P. Susceptibility, resistance development, and synergy of antimicrobial cile. Current Microbiology. combinations against Clostridium diffi 1982; 7: 59-62. 8. Poilane, I., Bert, F., Cruaud, P., Nicolas-Chanoine, MH., Collignon, A. Interest of the disk diffusion method for screening cile isolates with decreased susceptibility to antibiotics. Clostridium diffi Pathologie Biologie (Paris). 2007; 55(8-9): 429-33. 9. Cattoir, V., Ould-Hocine, ZF., Legrand, P. Antimicrobial susceptibility of Clostridium cile clinical isolates collected from 2001 to 2007 in a French diffi university hospital. Pathologie Biologie (Paris). 2008; 56(7-8): 407-11. 10. Brazier, JS., Levett, PN., Stannard, AJ., Phillips, KD., Willis, AT. Antibiotic susceptibility of clinical isolates of clostridia. Journal of Antimicrobial Chemotherapy. 1985; 15(2): 181-5. 1,5 1,5 1,5 7-10 1,5 1,5 1 2 6

Effective against serious Effective against infections including: C.diffi cile with C.diffi implicated Rarely Widely distributed throughout the body, including CSF including the body, throughout distributed Widely levels to i.v. comparable Oral levels C.diffi cile C.diffi E. coli Legionella Rickettsia MRSA VRSA Neisseria H. infl uenzae H. infl Typhoid

For further information, please contact: Essential Generics, 7 Egham Business Village, Crabtree Road, Egham, Surrey TW20 8RB, UK For further information, please contact: Essential Generics, 7 Egham Business Village, Crabtree Road, Abbreviated Prescribing Information Chloramphenicol Capsules BP 250mg Presentation: Hard Gelatin Capsules. particularly Indications: Typhoid fever and life-threatening infections, uenzae, where other antibiotics will those caused by Haemophilus Infl ce. not suffi Posology: For oral administration. doses. For Adults and elderly: 50 mg/kg body weight daily in 4 divided be doubled severe infections (meningitis, septicaemia), this dose may Children: initially, but must be reduced as soon as clinically possible. Not recommended. Contra-indications: Known hypersensitivity or toxic reaction to used chloramphenicol or to any of the excipients. Should not be active for the prophylaxis or treatment of minor infections; during liable to immunisation; in porphyria patients; in patients taking drugs by breast- depress bone marrow function; during pregnancy, labour or feeding mothers. Special warnings and precautions for use: Use only if other treatments are ineffective. Use should be carefully monitored. Reduce dose and monitor plasma levels in hepatic or renal impairment; in the elderly; and in patients concurrently treated with interacting drugs. Interactions: Chloramphenicol prolongs the elimination, increasing the blood levels of drugs including warfarin, phenytoin, sulphonylureas, tolbutamide. Doses of anticonvulsants and anticoagulants may need to be adjusted if given concurrently. Complex effects (increased/ decreased plasma levels) requiring monitoring of chloramphenicol plasma levels have been reported with co-administration of penicillins and rifampicin. Paracetamol prolongs chloramphenicol half-life. Chloramphenicol may increase the plasma levels of calcineurin inhibitors e.g. ciclosporin and tacrolimus. Barbiturates such as phenobarbitone increase the metabolism of chloramphenicol, resulting in reduced plasma chloramphenicol concentrations. In addition, there may be a decrease in the metabolism of phenobarbitone with concomitant chloramphenicol use. There is a small risk that chloramphenicol may reduce the contraceptive effect of oestrogens. Chloramphenicol reduces the response to hydroxocobalamin. Chloramphenicol is contra-indicated in patients taking drugs liable to suppress bone marrow function e.g. carbamazepine, sulphonamides, phenylbutazone, penicillamine, cytotoxic agents, some antipsychotics including clozapine and particularly depot antipsychotics, procainamide, nucleoside reverse transcriptase inhibitors, propylthiouracil. Pregnancy and Lactation: The use of chloramphenicol is contra- indicated as the drug crosses the placenta and is excreted in breast milk. cant effect Effects on ability to drive and use machines: No signifi on driving ability. Undesirable Effects: Reversible dose related bone marrow depression, irreversible aplastic anaemia, increased bleeding time, hypersensitivity reactions including allergic skin reactions, optic neuritis leading to blindness, ototoxicity, acidotic cardiovascular collapse, nausea, vomiting, glossitis, stomatitis, diarrhoea, enterocolitis, Gray Baby Syndrome particularly in the newborn, which consists of abdominal distension, pallid cyanosis, vomiting, progressing to vasomotor collapse, EG/CH/DEC/2015/10 00536_Chloramphenicol Ad_Microbiology Today_AW.indd 1 43:1 February 2016 43:1 February

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Microbiology Today 43:1 February 2016 Fungal Diseases