39:4 Nov 2012

Micro biology

TodayQuarterly Magazine of the Society for General Microbiology

Antimicrobials • Antibiotic discovery then and now • Biosynthetic potential of Actinobacteria • Waging war on fungi

• Enzybiotics and phages • Drugs fromMicrobiology bugs Todaythat Nov kill 2012 bugs1 • Flying the flag for ‘Antibiotic Action’ 22337_Chloramphenicol Ad_Micro Today_AW:1 11/4/12 17:10 Page 1 CHLORAMPHENICOL

Widely distributed throughout the body, including CSF1 Editorial Oral levels comparable to i.v. levels2

3 Rarely implicated with C.difficile

Effective against serious infections including: H. influenzae1,2 Typhoid1,2 Welcome to the November issue MRSA4 of Microbiology Today. This issue is VRSA5 Neisseria1,2 focused on a subject very close to Legionella1,2 Rickettsia1,2 my heart – antimicrobials. C.difficile6-9 In 2009, the World Health Organization access the biosynthetic potential of 1 E. coli recognised that antibiotic resistance actinomycete bacteria using a range of was one of the three greatest threats to modern molecular biology techniques, human health. In this issue, we discuss with the potential to access new some of the issues related to antibiotics, antibiotics (p. 204). Abbreviated Prescribing Information respiration and death within a few hours of the onset of symptoms. Chloramphenicol Capsules BP 250mg Overdose: Stop chloramphenicol immediately if signs of adverse their use and discovery. I’d also like to take this opportunity events develop. Treatment is mainly supportive. If an allergy develops, Julian Davies introduces the subject to thank Hilary Lappin-Scott for all her Presentation: Capsules containing 250mg chloramphenicol BP. oral antihistamines may be used. In severe overdosage e.g. Gray Baby Indications: Typhoid fever and life-threatening infections, particularly Syndrome, reduce plasma levels of chloramphenicol rapidly. Resin with a discussion of antibiotic discovery help and support for Microbiology those caused by Haemophilus Influenzae, where other antibiotics will haemoperfusion (XAD-4) has been reported to substantially increase not suffice. chloramphenicol clearance. and how this has changed since the Today during her presidency and to wish Posology: For oral administration. Pack size and Price: 60 capsules £377.00 Adults and elderly: 50mg/kg body weight daily in 4 divided doses. Legal Category: POM. days of Fleming and Waksman (p. 200). Nigel Brown every success in his new For severe infections (meningitis, septicaemia), this dose may be Market Authorisation Number: PL17736/0075. doubled initially, but must be reduced as soon as clinically possible. Market Authorisation Holder: Chemidex Pharma Limited, 7 Egham Patricia Veiga-Crespo and Tomas Villa role as President. I also used this change Children: Not recommended. Business Village, Crabtree Road, Egham, Surrey TW20 8RB, UK. Contra-indications: Known hypersensitivity or toxic reaction to Date of preparation: April 2012. cover the use of bacteriophages and in presidency to solicit articles from chloramphenicol or to any of the excipients. Should not be used See Chloramphenicol Summary of Product Characteristics for full for the prophylaxis or treatment of minor infections; during active prescribing information. enzymes derived from bacteriophages both! It is encouraging to see SGM immunisation; in porphyria patients; in patients taking drugs liable in food, where they suggest there is taking a proactive role in promoting to depress bone marrow function; during pregnancy, labour or by breast-feeding mothers. Adverse events should be reported. Reporting forms and great potential for this technology diversity awareness in microbiology Special warnings and precautions for use: Use only if other treatments information can be found at www.mhra.gov.uk/yellowcard. are ineffective. Use should be carefully monitored. Reduce dose and (p. 212). To tackle issues in fungal (see ‘Marjory Stephenson and me’ by monitor plasma levels in hepatic or renal impairment in the elderly and Adverse events should also be reported to Essential in patients concurrently treated with interacting drugs. Generics on 01784 477167. infection, Neil Gow tells us about a new Hilary on p. 229) and what we hope Interactions: Chloramphenicol prolongs the elimination, increasing the blood levels of drugs including warfarin, phenytoin, sulphonylureas, strategic award from the Wellcome will be a regular feature from Nigel as tolbutamide. Doses of anticonvulsants and anticoagulants may need to References be adjusted if given concurrently. Complex effects (increased/decreased 1. Sweetman S.C. (ed), Martindale: The Complete Drug Reference. Trust to the University of Aberdeen is President (p. 193). plasma levels) requiring monitoring of chloramphenicol plasma levels [online] London: Pharmaceutical Press have been reported with co-administration of penicillins and rifampicin. (Accessed on 22 August 2011). to lead a pan-UK consortium in medical I hope you, the readers, will

Paracetamol prolongs chloramphenicol half-life. Chloramphenicol may 2. Feder, H. Chloramphenicol: What we have learned in the last Decade. 22337 mycology (p. 208), and Laura Piddock also appreciate the new format of increase the plasma levels of calcineurin inhibitors e.g. ciclosporin Southern Medical Journal. 1986; 79(9): 1129-34. 3. Kelly, C., LaMont, T. and tacrolimus. Barbiturates such as phenobarbitone increase Patient information: Antibiotic-associated diarrhea (Clostridium difficile). and Tracey Guise provide an update Microbiology Today, the SGM staff, the metabolism of chloramphenicol, resulting in reduced plasma www.uptodate.com. (Accessed on 11 August 2011). 4. Fluit, A.C., chloramphenicol concentrations. In addition, there may be a decrease Wielders, C.L.C., Verhoef, J., and Schmitz, F.J. Epidemiology and on the first year of Antibiotic Action in particular Ian Atherton and Dariel in the metabolism of phenobarbitone with concomitant chloramphenicol Susceptibility of 3,051 Staphylococcus aureus Isolates from 25 use. There is a small risk that chloramphenicol may reduce the University Hospitals Participating in the European SENTRY Study. and the great strides it has made in its Burdass, have worked incredibly hard contraceptive effect of oestrogens. Chloramphenicol reduces the Journal of Clinical Microbiology. 2001; 39(10): 3727-3732. 5. Weigel LM response to hydroxocobalamin. Chloramphenicol is contra-indicated et al. High-Level Vancomycin-Resistant Staphylococcus aureus (VRSA) first 12 months (p. 239). Helge Bode on the new design, based on what you, in patients taking drugs liable to suppress bone marrow function Associated with a Polymicrobial Biofilm. Antimicrobial Agents and e.g. carbamazepine, sulphonamides, phenylbutazone, penicillamine, Chemotherapy. Published online ahead of print on 30 October 2006. discusses his work on exploring the the membership, told us. In addition, cytotoxic agents, some antipsychotics including clozapine and http://aac.asm.org/cgi/reprint/AAC.00576-06v1.pdf. (Accessed on particularly depot antipsychotics, procainamide, nucleoside reverse 22 August 2011). 6. Ensminger, P., Counter, F., Thomas, L., Lebbehuse, symbiotic relationships between bacteria you will notice the slight adjustments transcriptase inhibitors, propylthiouracil. P. Susceptibility, Resistance Development, and Synergy of Antimicrobial

Essential Generics: Chloramphenical Ad and nematodes that kill insects and to content. I hope you enjoy this issue Pregnancy and Lactation: The use of chloramphenicol is contra-indicated Combinations Against Clostridium difficile. Current Microbiology. as the drug crosses the placenta and is excreted in breast milk. 1982; 7: 59-62. 7. Poilane, I., Bert, F., Cruaud, P., Nicolas-Chanoine, how this has led to the discovery of new and we look forward to hearing any Effects on ability to drive and use machines: No significant effect MH., Collignon, A. Interest of the disk diffusion method for screening on driving ability. Clostridium difficile isolates with decreased susceptibility to antibiotics. natural products that have therapeutic thoughts on the new design. Undesirable Effects: Reversible dose related bone marrow depression, PathologieBiologie (Paris). 2007; 55(8-9): 429-33. 8. Cattoir, V., irreversible aplastic anaemia, increased bleeding time, hypersensitivity Ould-Hocine, ZF.,Legrand, P. Antimicrobial susceptibility of Clostridium potential (p. 216). reactions including allergic skin reactions, optic neuritis leading to difficile clinical isolates collected from 2001 to 2007 in a French CAPSULES blindness, ototoxicity, acidotic cardiovascular collapse, nausea, vomiting, university hospital. PathologieBiologie (Paris). 2008; 56(7-8): 407-11. Finally, I contributed to this PAUL A. HOSKISSON, Editor

glossitis, stomatitis, diarrhoea, enterocolitis, Gray Baby Syndrome 9. Brazier, JS., Levett, PN., Stannard, AJ., Phillips, KD., Willis, AT. mm Bleed: 3 mm Supply as hi-res PDF Job no: particularly in the newborn, which consists of abdominal distension, Antibiotic susceptibility of clinical isolates of clostridia. Journal of PIP: 106-5796 issue myself, describing how we can Email [email protected] 210

EG/CH/APR/2012/08 pallid cyanosis, vomiting, progressing to vasomotor collapse, irregular Antimicrobial Chemotherapy. 1985; 15(2): 181-5. x

AAH: CHL600B 297 ALLIANCE: O65995 2 Microbiology Today Nov 2012 Microbiology Today Nov 2012 189 Trim size: Trim Journal: Microbiology Today Journal: Microbiology Today MOVIANTO: CHL25060 For further information, please contact: Essential Generics, 7 Egham Business Village, Crabtree Road, Egham, Surrey TW20 8RB, UK Contents SGM Council 12/13 MICROBIOLOGY TODAY 39:4 NOV 2012 articles www.sgm.ac.uk/pubs/micro_today

200 Antibiotic Executive Officers discovery: then and President – Professor Nigel L. Brown now c/o Society for General Microbiology, Marlborough House, features Basingstoke Road, Spencers Wood, Reading RG7 1AG julian davies Tel. 0118 988 1801; Email [email protected] The fascinating story behind the history General Secretary – Professor David J. Blackbourn of antibiotics 189 Editorial 228 Interview Defra Chief University of Birmingham, Cancer Research UK Institute for Cancer Scientific Advisor Ian Boyd Studies, Edgbaston, Birmingham B15 2TT 193 From the President Tel. 0121 415 8804; Email [email protected] 231 Marjory Treasurer – Professor Colin R. Harwood Schoolzone – 220 Stephenson and Centre for Bacterial Cell Biology, Institute for Cell and Molecular 204 Accessing Answers to the most Biosciences, Baddiley Building, University of Newcastle, Newcastle upon the biosynthetic me Hilary Lappin-Scott common questions about Tyne NE2 4AX discusses ‘diversity’ in Tel. 0191 208 3221; Email [email protected] potential of antibiotics are provided in microbiology Chairs of Committees Actinobacteria ‘Antibiotics in action’ , and PAUL A. HOSKISSON Communications Committee – Professor Joanna Verran Ian Richardson & Annabel 232 SGM journals See Department of Biology, Chemistry and Health Science, Manchester Can bacteria still provide a Large describe how they what the SGM journals Metropolitan University, Chester Street, Manchester M1 5GD source of desperately needed got in touch with SGM offer and, in addition in Tel. 0161 247 1206; Email [email protected] novel antimicrobials? and used the Microbiology this issue, Guest Editor Finance Committee – Professor Colin R. Harwood (see ‘Treasurer’ above) Twitter Journal Club as Rocky Cranenburgh Cover Ciprofloxacin antibiotic pill in a Professional Development Committee – Dr Sara Burton blister pack. Tek Image / Science Photo Library Geoffrey Pope Building, University of Exeter, Stocker Road, Exeter part of Annabel’s research invites papers for the July EX4 4QD in ‘A taste of honey’ 2013 special issue of Tel. 01392 263437; Email [email protected] Microbiology on SynBio Policy Committee – Professor Nigel L. Brown (see ‘President’ above) 224 Journal publishing Publications Committee – Professor Charles Penn Karen McGregor presents 236 Society of Biology School of Biosciences, University of Birmingham, Edgbaston, the second part of her Open Education Editor Birmingham B15 2TT 208 Waging 212 Enzybiotics Dr Paul A. Hoskisson Tel. 0121 414 6562; Email [email protected] war on fungi and phages: safe article looking this time at Resources Eva Sharpe Scientific Conferences Committee – Dr Evelyn M. Doyle the publisher’s viewpoint relates how SB recently Managing Editor and Design School of Biology & Environmental Science, University College, – the unknown alternatives to received funding from the Ian Atherton Ardmore House, Dublin 4, Republic of Ireland Opportunities superbugs antibiotics in the 226 HE Academy and JISC Editorial Assistant Tel. +353 1 716 1300; Email [email protected] Neil A.R. Gow & control of food safety for UG students Yvonne Taylor Elected Members others PATRICIA VEIGA-CRESPO & SGM support for 239 Comment Tracey Address SGM, Marlborough House, Basingstoke Professor Andrew Davison MRC-University of Glasgow Centre for Mycology researchers are TOMAS G. VILLA undergraduates Guise & Laura Piddock Road, Spencers Wood, Reading RG7 1AG Virus Research, Church Street, Glasgow G11 5JR starting to fight back ‘fly the flag’ for Antibiotic Tel. 0141 330 6263; Email [email protected] Can phages be used to eliminate the use of Tel. 0118 988 1842 Email [email protected] Action Professor Ian R. Henderson Division of Immunity & Infection, antibiotics in animal feed? © 2012 Society for General Microbiology University of Birmingham Medical School, Edgbaston, Birmingham B15 2TT ISSN 1464-0570 Tel. 0121 414 4368; Email [email protected] Printed by Latimer Trend & Co. Ltd, Dr Paul A. Hoskisson Strathclyde Institute of Pharmacy & Biomedical 216 Drugs from Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE bugs that kill bugs reguLars Plymouth Tel. 0141 548 2819; Email [email protected] HELGE B. BODE Dr Karen Robinson Centre for Biomolecular Sciences, University of Bioactive compounds Nottingham, University Park, Nottingham NG7 2RD 194 News Tel. 0115 823 1094; Email [email protected] from insect-pathogenic bacteria? Professor John H. Sinclair Department of Medicine, Level 5, Laboratory 196 Conferences The views expressed by contributors do not Block, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 0QQ necessarily reflect official policy of the Society; Tel. 01223 336850; Email [email protected] 198 Microshorts nor can the claims of advertisers be guaranteed. Professor Maggie Smith Department of Biology, University of York, society for general Wentworth Way, York YO10 5DD 237 Reviews Tel. 01904 328500; Email [email protected] Microbiology

190 Microbiology Today Nov 2012 Microbiology Today Nov 2012 191 from the president Small volumes can make The Thermo Scientifi c VersaTREK Automated Microbial Detection System is the only two-bottle media system cleared by the U.S. FDA for blood draws as low as 0.1mL. This unique platform provides both aerobic and anaerobic microbial detection without the need for costly It is a great privilege to have been on Sexually Transmitted Infections, specialty media. Designed to help you improve patient care, the easy-to-use VersaTREK System and in influencing scientific opinion- elected President of the Society for formers in Government, funding enables you to increase recovery and decrease cost at the same time—because complex agencies and elsewhere. Our previous policy statement on Food Security challenges require uncompromised solutions. General Microbiology in September and and Food Safety was well received by I look forward to serving the Society and parliamentarians and other opinion- formers. The SGM presented the policy a big difference its members over the next 3 years. to the Government’s Food Research Partnership. In this issue (p. 226), there is an interview with Professor Ian Boyd, It is a time of great change in the members’ database, allowing us to recently appointed Chief Scientific external environment for learned be more responsive and tailored to Adviser to Defra, following similar societies, and Council and the members’ needs. • To learn more, visit thermoscientifi c.com/versatrek articles with the European CSA and the Marlborough House staff will be These internal changes are just UK Government CSA. working hard to ensure that the the start. We have restructured the During my Presidency, I plan Society continues to be successful. Committees of Council to serve the for the SGM to engage much more We will have to meet the demands of new Strategic Plan; we are currently strongly with Government and public open access publication that UK funders in the process of electing members bodies, to better represent the discipline are asking for, yet maintain the journal to these Committees. The Education of microbiology and to ensure that the income to support our conferences, and Public Affairs Committee and relevant science is taken into account our educational provisions, and our Education Division have been reformed in decision-making. Where appropriate, many other activities. We have to into the Communications Committee this will be done in partnership with continue to provide member benefits and Professional Development other learned societies. The issues that are valued. Committee to serve the external of emerging infectious disease, This would at least maintain the educational environment (schools, antimicrobial resistance, vaccination, status quo, but there is much more that public engagement, etc.) and to help in and a number of other scientific topics the Society needs to do. The Society the continued professional development relevant to our discipline require started to modernise its practices under of our members. In particular, we continual engagement by members, Hilary Lappin-Scott and the appointment are concerned with the issues of and relatively new developments, such of Simon Festing as Chief Executive has development of early-career researchers as synthetic biology, require us to make accelerated the process. This progress and ensuring that we promote equality the scientific information more widely will continue going forward. We have and diversity. As outgoing President, known. appointed a new Publications Manager Hilary Lappin-Scott has written on I look forward to leading the who will bring forward a publications gender diversity in the profession in this Society through these exciting times strategy for Council’s consideration. A issue (p. 229), and Council has asked and would like to hear from any new website will be launched early in her to be the SGM Diversity Champion. members who are keen to support 2013, which will be more up-to-date The Policy Working Group has these endeavours. and user-friendly than the current site. become the Policy Committee and is Marlborough House staff will have engaged in responding to consultations, NIGEL L. BROWN, President the benefit of working with a new in developing a policy statement Email [email protected]

192 Microbiology Today Nov 2012 Microbiology Today Nov 2012 193 © 2012 Thermo Fisher Scientifi c Inc. All rights reserved. c Inc. All rights reserved. © 2012 Thermo Fisher Scientifi © 2012 Thermo Fisher Scientifi c, Inc. All rights reserved. All trademarks are the property of Thermo Fisher Scientifi c, Inc. c, of Thermo Fisher Scientifi the property All trademarks are Inc. All rights reserved. c, © 2012 Thermo Fisher Scientifi party and licensed to owned by a third and its subsidiaries. Copyrights in to the photograph are c by Veer. Thermo Fisher Scientifi

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News of Members Success for SGM CARA SGM at ASE Malaria resource Congratulations to… grant recipient In January 2013, we will be returning to the Our long awaited fact file Malaria: A Association for Science Education (ASE) Conference Global Challenge is now available to order STEM Ambassador Mark Fernandes (IFR, Norwich) who Supporting professional development of in Reading. from our website: www.microbiology has won the CUE East Award for Individual Achievement for his microbiologists is one of the core strands of SGM online.org.uk/teachers/resources. outstanding contribution to public and community engagement; strategy and, in 2011, Council decided to add a new Tom Ellis (Imperial College London) will Ross Fitzgerald who has been appointed Chair in Molecular dimension to this by offering sponsorship to the be giving a talk on synthetic biology as part of Members are welcome to contact Bacteriology at the University of Edinburgh; Council for Assisting Refugee Academics (CARA), an Biology in the Real World, James Redfern and John our Education & Outreach Officer Vicki Schollar will be giving practical advice, and the SGM Symington ([email protected]) for Ian Poxton (University of Edinburgh) on receiving a lifetime organisation which provides much-needed financial team will be in the exhibition tent (free entry!). If multiple copies for education or outreach achievement award from the Anaerobe Society of the Americas assistance to microbiologists who have come to the you are going along, drop by to say ‘hello’! activities. for his contribution and dedication to the field of anaerobic UK as refugees escaping persecution. microbiology. The first grant recipient was Nadje*, who has a PhD committee, and the first and longest The Society notes with regret the passing of Dr Derek J. in Microbiology from the University of Salahaddin, serving Editor of the Journal of General Barbara (member since 1973), PROF. Howard GEST (member Erbil, Iraq, and 10 years experience of teaching and Microbiology. He also gave the Marjory since 1956) and Prof. Robin J. Rowbury (member since 1964). supervising students. She is now paving her way to Stephenson Memorial Lecture in 1961. becoming a clinical scientist in the UK. Using the On retirement in 1969 he was made an funds, she was able to enrol on the MSc in Molecular Part 2 Microbiology Honorary Member of the Society. Biology of Infectious Diseases at the London School Prize winner continues of Hygiene and Tropical Medicine in September This association with SGM was maintained by Knight’s successor to excel 2011, for which she immediately expressed her Colin Kaplan as joint founding Editor , gratitude; ‘I have got the experience and skills and David Taylor of the Journal of General Virology, who was awarded the this is my opportunity to get my life and my career and this continued through his SGM prize for the best back on track’. Guests at the 60th anniversary celebrations. University of Reading successor Jeff Almond (Fleming Lecturer, performance in his Part 2 Najde enjoyed the course and performed well 60 years of Microbiology at Reading 1985), Jane McKeating (Fleming Microbiology Modules at while looking after her two young children. She Well over 100 alumni and other former plaque was unveiled by a member of Lecturer, 1995) and John Grainger the University of Reading, even found time for voluntary laboratory work at and current Reading microbiologists his family, and those present signed the (Peter Wildy Prize Lecturer, 2002). has continued to excel St George’s Hospital during the summer of 2012 to gathered on 7 September 2012 to Visitors’ Book which contains previous The former Department of in his studies and has supplement her CV. The MSc finished with a research celebrate the 60th anniversaries of entries from six Nobel Laureates, half Microbiology, now within the gone on to win the Part project with the support of Nick Dorrell’s group. the founding at Reading of the first of the past Presidents of SGM and HM 3 Biomedical Project Prize School of Biological Sciences, About CARA university Department of Microbiology the Queen who formally opened the in 2012 for his project on maintains vigorous research CARA will celebrate its 80th anniversary in 2013 in the UK in 1951 and the introduction building in 1992. ‘The role of M protein in programmes in bacteriology and and remains an organisation run by academics of the degree course in microbiology torovirus assembly’ with ‘Gabe’ Knight came to Reading with virology, and continues to provide a working on behalf of fellow academics in need, in 1952. SGM was represented by Dr Ben Neuman. David an international reputation in microbial BSc course in microbiology which who are all too often amongst the first to be Jane Westwell. A series of talks was is pictured here with nutrition and recognition for the first includes a field course in Iceland. targeted by state-sponsored violence and repression. followed by a reception and a ceremony Professor G. Brooks, the demonstration of an enzymic activity in For further details see www.reading. to re-name the microbiology building Pro-Vice-Chancellor for SGM was the first learned society to engage in a a bacterial toxin, i.e. Clostridium welchii ac.uk/news-and-events/releases/ as the Knight building to honour the Teaching and Learning formal partnership to offer financial support that is (now perfringens) α-toxin. He made a PR464056.aspx Foundation Professor B.C.J.G. (Gabe) at the University of committed to a specific academic discipline. significant contribution to the founding Knight (1904–1981). A ceremonial John Grainger Reading. *Nadje is an alias to protect the grant recipient’s identity. of SGM, was a member of its first David Butlin, University of Reading

194 Microbiology Today Nov 2012 Microbiology Today Nov 2012 195 conferences

SGM Spring Conference 24–28 March 2013

SYMPOSIA Manchester Central Convention Complex – www.sgmmanchester2013.org.uk – Viruses and human cancer: causes to cures – RNA – so much more than just a genome Submit your abstract and be part of the SGM Spring Conference 2013. SGM Prize Medal Lecture to be delivered by Nobel-Prize- – Co-infections & co-colonisation Register to network at Europe’s largest annual gathering of microbiologists. Winning Virologist Harald zur Hausen. – New approaches to exploit Streptomyces Conference snApShot – Next-generation antimicrobials – Antimicrobial resistance: are scientists getting Metabolic interactions at the host–pathogen interface Bacterial–fungal interactions Networking workshop for early-career delegates the message right? (25–26 March 2013) (27–28 March 2013) (24 March 2013) Despite global efforts, diseases such as malaria, sleeping sickness Bacterial–fungal interactions play a Conferences are all about communicating with other scientists, virology workshops and tuberculosis still affect up to half a billion people each year, pivotal role in agricultural and forestry either formally when presenting research or informally when you – Vaccines and antivirals | Viromics | Assembly and and cause more than 2 million deaths. New drugs to combat ecosystems, in food spoilage and plant network with other researchers during breaks, poster sessions structure | Innate immunity | RNA – so much more these diseases are urgently needed. Drugs targeting essential disease, and in infection of human or after the conference sessions close. Conferences also offer than just a genome | Pathogenesis | Replication | steps in pathogen metabolism represent a promising and relatively and animal hosts. They also have a networking opportunities which can lead to fresh ideas, a new Clinical virology unexplored approach for disease control. wide range of applications from collaboration or maybe even your next job. prize medal lecture biocontrol and bioremediation through There is increasing evidence that the nutritional environment within Why attend – To be delivered by Nobel-Prize-winning virologist to food and drink production and host tissues has a major impact on pathogen growth and virulence, Professor Harald zur Hausen. the production of novel high-value The networking workshop and supper brings together early-career and that pathogens are able to manipulate host metabolism to chemicals. delegates before the start of the conference. Delegates who attend promote infection. key dates get to know some friendly faces and also pick up tips and advice on Why attend – Monday 14 January 2013 (noon): Why attend making the most of networking opportunities during the following Speakers from a wide range of fields abstract submission closes days. The session is highly recommended by previous delegates: Speakers at this symposium will review our current understanding will explore the mechanisms, impact – Friday 22 February 2013: of metabolic interactions at the host–pathogen interface, and and applications of bacterial–fungal ‘…The skills we learnt in the networking event made me feel more earlybird registration closes discuss the prospects of using knowledge of metabolic interactions interactions. The symposium will confident in approaching other researchers. Being at a conference grants available foR: between host and pathogen to develop novel strategies for disease include a presentation by Reid Harris and having the chance to talk face to face with other researchers control. In particular, Henri Vial (Université Montpellier II), Mike (Virginia Tech, USA) on biocontrol in your area really improves your relationship with them and it – Associate Members who are postgraduate Barrett (University of Glasgow) and Bill Hunter (University of of Chytridiomycosis, an extremely shortcuts communications compared to building up a relationship students, retired or technicians Dundee) will explore metabolic targets for disease control. damaging disease of amphibians. by email…’ – Qualifying Undergraduate Student Members Save the dates SGM Autumn Conference 2013, SGM Spring Conference 2014 University of Sussex Arena and Convention Centre Liverpool 2–4 September 2013 14–17 April 2014 Symposia Other SGM-sponsored scientific meetings Microbial subversion of the host | Microbial survival in the host | Fungal diseases, Recent Independent Virology Researchers’ diagnostics & drug discovery | Emerging fungal (RIVR) Meeting 3–4 January 2013, Marriott pathogens | Impact of phage | Regulatory Breadsall Priory, Derby phosphate-based molecules | Sustainability of CRISPR: Evolution, Mechanisms and Infection microbiology as a profession 17–19 June 2013, University of St Andrews Manchester Central

196 Microbiology Today Nov 2012 Microbiology Today Nov 2012 197 micro shorts

Bacteria ‘mite’ cause rosacea Super-sensitive biosensor enhances virus detection Rosacea, a common skin disease, is A sensor that can detect the smallest known viruses has been enabling detection of minute changes in resonant created. It works by sending light waves resonating at a specific frequency. The gold sensor meant even the tiny MS2 primarily caused by bacteria, aided by Rosacea. Demodex folliculorum mites that live in CNRI / Science Photo Library frequency within a glass sphere; the presence of a virus changes virus, which is 1% of the mass of the influenza A the resonant frequency of the light within the sphere. Researchers virus, could be detected. This development holds Microbes and JMM the skin, according to a new review. The findings should lead to more targeted treatments for from the Polytechnic Institute of New York University called the enormous potential for early identification and metabolism the condition. Rosacea, characterised by inflammation sensor the Whispering Gallery-Mode Biosensor after the circular treatment of disease. The gut microbiota of women has and lesions in the central regions of the face, affects gallery in St Paul’s Cathedral, where someone whispering near the Applied Physics Letters doi:10.1063/1.4739473 wall can be heard around the gallery. The sensitivity of the sensor been shown to change dramatically nearly 3% of the population and is more common Daniel Amund London Metropolitan University during the course of pregnancy, and in women than in men. High densities of Demodex was increased by attaching gold nanoparticles to the glass sphere, by the third trimester the composition mites are common in patients suffering from rosacea. resembles that seen in some Bacillus oleronius has been isolated from the gut of Antimicrobial essential oils – not to be sniffed at inflammatory gut disorders. The Demodex mites from rosacea patients. It is speculated Plant-derived essential oils show greater toxicity against pathogenic micro- work sheds light on the complex that the proteins released by B. oleronius, upon organisms compared to commensal gut bacteria, according to a new study. The relationship between the gut microflora death of the mite, stimulate an immune response work contributes to the development of essential oils as health-enhancing food and host metabolism. A Finnish that triggers rosacea. Further research on the role of additives to treat or prevent colonic microbial imbalances. Researchers from the study collected stool samples, diet these bacteria and Demodex mites will help shed light University of Aberdeen found that the essential oils from cloves, coriander, information and clinical data from 91 into the pathogenesis of the disease and could lead curcuma and geranium, and their purified chemical components, exhibited pregnant women. The microbiome to novel ways to prevent and control rosacea. different growth-inhibitory effects, depending on their chemical characteristics. was more diverse during the first JMM doi:10.1099/jmm.0.048090-0 Pathogenic gut bacteria such as Escherichia coli O157:H7 and Clostridium difficile were, in general, more sensitive to the essential oils and their constituents than the trimester with a profile similar to that Sruthi Raghavan Freelance writer for healthy individuals. However, by commensal strains. The inhibitory effect was shown not to be due to membrane the third trimester the diversity was Could bacteria solve our energy needs? damage. While these results show great promise, further optimisation, including generally reduced and the relative studies using mixed cultures and in vivo, is required in order to ensure the Scientists have shown that the energy bacteria produce while degrading abundance of Proteobacteria, which protection of beneficial commensal strains. wastewater can be harvested to make electricity. Capturing this source would are associated with inflammatory Microbiology doi:10.1099/mic.0.061127-0 create a new energy supply and avoid the consumption involved in wastewater Coriander. conditions such as inflammatory treatment, according to recent review of the topic. In the US, 3% of all electrical Microbiology Mireille Vankemmelbeke University of Nottingham iStockphoto / Thinkstock bowel disease, was significantly higher. power is used in wastewater treatment. However, When the microbiota from the third this wastewater also has huge energy potential. New Unlikely commensals: wasps and yeasts trimester of pregnancy was transferred technologies use bacteria to catalyse electrochemical Wasps are an important reservoir and vector of many yeast strains, including into germ-free mice, this induced reactions using waste organic matter as a substrate. Saccharomyces cerevisiae, according to a new study. Researchers recognised that pregnancy-like metabolic changes. The most studied electrogenic organisms are yeasts found in nature, such as those associated with grapes, could be readily Importantly, this work suggests that Geobacter and Shewanella species, though many isolated from their environment during the warmer months. However, where the the host microbiota impacts host others could also be used. Research is currently yeasts resided in the autumn and winter was unclear. The University of Florence metabolism during pregnancy by taking place to assemble bacterial communities research team suspected that wasps may carry yeasts in their gut because they fed promoting the storage of energy that can produce electricity by degrading the complex on grapes and other fruits during summer. To test their theory, they isolated the in fat tissue, which is beneficial to mixture of compounds found in wastewater. At microflora from the guts of hornets, wasps and honeybees from different locations support growth of the foetus. the moment, it is cheaper to produce electricity in the Italian countryside. Wasps were found to harbour yeast strains during the However, in non-pregnant individuals through traditional methods rather than microbial winter, and actually transmit yeasts to their offspring. This work helps shed light this increases the risk of type 2 technologies. However, as fossil fuels become more on the natural history of yeasts, which remains poorly understood despite their diabetes and is associated with scarce, microbial technologies are likely to prove a importance in food and beverage production and molecular biology. disease states. viable alternative. PNAS doi:10.1073/pnas.1208362109 Cell doi:10.1016/j.cell.2012.07.008 Science doi:10.1126/science.1217412 Jessica Blair University of Birmingham Greg Potter Dalhousie University, Canada Lena Ciric University College London

Wastewater. Wasp feeding on a plum. Stockbyte / Thinkstock iStockphoto / Thinkstock

198 Microbiology Today Nov 2012 Microbiology Today Nov 2012 199 Albert Schatz (1920–2005) who discovered Julian Davies streptomycin, photographed in 1943. Special Collections and University Archives, Rutgers University Libraries Antibiotic

The presence of antimicrobial lives in the battles following D-Day agents has been known since the days and in the Japanese campaigns. These of Louis Pasteur – who else? When discovery: two antibiotics were discovered with very Pasteur and Joubert described the primitive, functional screens, the kind phenomenon of bacterial antagonism that can be done in secondary school in 1877, they noted that the growth of classes anywhere nowadays. Of course, Bacillus anthracis was restricted in the the essential discovery process was to presence of other bacterial strains and then and isolate, purify and characterise the active commented that such activity might well compound(s) and show that they are be of therapeutic value. Somewhat later, novel, active and non-toxic. in 1928, Papacostas and Gaté described a A critical element in the number of examples of the phenomenon, introduction of antibiotics during the involving different bacterial genera and now early days of antibiotic discovery was species. They presented this phenomenon the mobilisation of the pharmaceutical as antibiosis and even used the word and fermentation industries in the ‘antibiotique’. However, it was not until There is much discussion about US and, subsequently, in the UK. As 1945 that Selman Waksman formalised more companies started looking for the name and defined an antibiotic as how we tackle the antibiotic crisis bacteria and fungi capable of producing a ‘chemical substance of microbial origin that active antibiotics, the actual discovery possesses antibiotic powers’. now and in the future, but the story process changed little, other than in It is now known that many organisms magnitude. Screening depended on produce chemicals with antibiotic activity of how we arrived at this point is manpower, and chemical identification and a number of such compounds can of potential candidate antibiotics was be made synthetically. The production just as fascinating. a slow business using the traditional of antibiotics and other compounds by approaches of natural products research. microbes was previously considered to Nonetheless, by the mid-1940s, in antibiotics have had greater value in other be a process of secondary metabolism addition to penicillin and its derivatives, medical applications; good examples are (usually triggered by signals in later stages the first antibiotic active in the cyclosporin and rapamycin (sirolimus) of growth and development). However, treatment of tuberculosis, streptomycin, that are active immunosuppressants given the fact that the products are in no was discovered by Albert Schatz in and have transformed the science of way secondary, the preferred description Waksman’s laboratory. Subsequent transplantation medicine. Original is ‘specialised metabolism’. ‘Antibiotic’ entries into the pharmaceutical arena In the late 1930s, the sulfonamides laboratory is synonymous with ‘antimicrobial’ included chloramphenicol, tetracycline, came onto the scene and they proved to sample of and the two are used interchangeably, erythromycin, lincomycin, polymyxin and be the first revolution in antimicrobial ‘M&B 693’ especially in the popular press. Most vancomycin; certainly hundreds of other therapy. This genuine target-based (1938), one are produced by streptomycetes, but of the first compounds discovered by Waksman- therapy (Ehrlich-style) was very successful; bacilli, pseudomonads and fungi all sulfonamide style screening failed to make the grade even though this class of compounds has produce a variety of therapeutically antibiotics. It because of insolubility, toxicity, instability, a limited spectrum of activity, these drugs active chemicals. Interestingly, the was used for serum binding, colour, smell, poor activity were used throughout the Second World pyocyanins, products of Pseudomonas treating spectrum, low yield or some other War – and still are! The golden age of spp., were used in the late 1800s, and pneumonia inadequacy. Screening for compounds antibiotic discovery began with the use of and gangrene. may have been the first antibiotics was routine and simple, every company penicillin and subsequently streptomycin Wellcome Library, employed clinically. It is worth noting isolated many candidates but few made at the end of the Second World War; London / Science that some chemicals discovered as the cut-off. penicillin was responsible for saving many Museum, London

200 Microbiology Today Nov 2012 Microbiology Today Nov 2012 201 The future discovery of new antibiotics and other“ therapeutic agents can now be envisaged as a process involving the identification of biosynthetic pathways for small molecules, and productive expression of the pathways by cloning into heterologous hosts or by metabolic activation.” As physicians throughout the world discontinued in the Western world; by sequencing of Streptomyces coelicolor, an faced increasing examples of recalcitrant the 1980s, most antibiotics were being antibiotic-producer, not a pathogen. infections due to the development of mass-produced in countries like India This, the largest bacterial genome to be resistance during treatment, the industry and China. sequenced at this time (~9.0 Mb), was made serious efforts to produce antibiotic In the late 1980s, a number of a real eye-opener since it revealed that derivatives with activity against resistant pharmaceutical companies made S. coelicolor, known to produce a small strains; this became more and more of a attempts to employ novel high- number of pigments and other bioactive losing proposition. Nonetheless, there were throughput methodologies to develop molecules, has in fact the genetic capacity Selman Waksman notable successes, for example methicillin screening processes enabling the to produce more than 20! Suddenly, the (1888–1973, centre), working with researchers (now meticillin) and other β-lactamase- identification of new antibiotic molecules, claims by pharmaceutical companies in his laboratory. National resistant penicillins and cephalosporins, but most of the efforts came up empty- about having discovered most of the Cancer Institute / Science Photo and even modified aminoglycosides. handed. There was even a belief that compounds available became fiction. It Library However, there was always an Achilles all of the accessible structural scaffolds became apparent that there are orders heel in the antibiotic structure and these for antibiotics had been uncovered. of magnitude more antibiotics and of small molecules, some of which have by cloning into heterologous hosts FURTHER READING successes were only temporary. Industrial antibiotic discovery reached other pharmaceutical agents available been identified as antibiotics. However, or by metabolic activation. Structure Bentley, S.D. & others (2002). Complete The development of resistance did a new low. However, the advent of the in nature. Complete genome sequencing these so-called antibiotics may actually determination can always be a problem genome sequence of the model actinomycete Streptomyces coelicolor A3(2). Nature 417, 141–147. not alone lead to the end of the ‘golden genome sequencing era in 1995 with the studies have revealed that a large number be used in nature as signalling agents. but newer physical methods and Davies, J. & Ryan, K.S. (2012). Introducing era’ of antibiotics. Regulatory authorities success of the Venter group in obtaining of microbial genera possess many hidden Support for this notion comes from the sophisticated instrumentation should the parvome: bioactive compounds in the fact that antibiotics at sub-inhibitory provide solutions. The compounds have demanded increasingly strict and the complete genome sequences of two biosynthetic pathways for bioactive microbial world. ACS Chem Biol 7, 252–259. concentrations can act as signalling obtained can then be detected, extended clinical trials for the protection bacterial pathogens triggered a new molecules: the huge phyla of Actinobacteria Hughes, D.T. & Sperandio, V. (2008). of the human population (especially wave of optimism in the industry since and Firmicutes, and the ‘Myxobacteria’, molecules to regulate transcription in purified and screened using sensitive Inter-kingdom signalling: communication between after the thalidomide disaster) and the it was thought that these sequences etc. The number is unimagineable. bacteria; at these concentrations, they transcriptional assays. bacteria and their hosts. Nat Rev Microbiol 6, 111–120. ability to meet all requirements has been would permit the identification of The question is how to exploit this influence multiple cellular activities. By exploiting the increasingly Papacostas, G. & Gaté, J. (1928). Les Associations difficult. In addition, microbes themselves novel, metabolism-based targets. Several information and obtain the compounds Studies of the mode of action of rapid and sensitive techniques for Microbiennes, Leur Applications Thérapeutiques. Paris: have shown genetic adaptability in industrial groups took this route, but the for investigation. antibiotics have revealed that their targets genome sequencing and bioinformatic Doin. ways not previously anticipated. The success rate was low and the products High-throughput metagenomic include the core functions in the cell: analysis, it will eventually be possible to Payne, D.J. & others (2007). Drugs for bad bugs: confronting the challenges of antibacterial first reports of transferable antibiotic lacked novelty. In addition, the inherent sequence analysis of microbial transcription, translation, replication and gain complete access to the parvome discovery. Nat Rev Drug Discov 6, 29–40. resistance in the late 1960s were greeted weakness of ‘designer’ chemical libraries populations (microbiomes) from diverse many aspects of metabolism. There is (the ‘-ome’ of the small chemical Pringle, P. (2012). ‘Experiment Eleven’. Dark Secrets increasing evidence that sub-inhibitory molecules produced by living organisms). with disbelief from the scientific and was at fault and the hit rate was very environments has raised awareness behind the discovery of a Wonder Drug. New York: antibiotics do not inhibit, but modulate This will transform drug discovery medical community. However, it is now disappointing. This led to additional Big that bacteria and other microbes Walker & Company. recognised as the major factor in the Pharma drop-outs from the field and do not live in isolation, but exist in these functions. For example, the and provide constant stimulation for Ryan, R.P. & Dow, J.M. (2008). Diffusible global spread of resistance and efforts the onus for antibiotic discovery fell on huge interactive communities. These antibiotic rifampicin, a well-characterised new pharmaceutical developments, signals and interspecies communication in to eliminate or prevent horizontal gene small biotech companies, most of which communities employ distributed inhibitor of RNA polymerase, actually especially those employing synthetic bacteria. Microbiology 154, 1845–1858. transfer have been totally unsuccessful. lacked the finance and personnel to take metabolic processes that are regulated stimulates the production of specific biology. Ventura, M. & others (2007). Genomics Why did the golden era end? It seems advantage of the increasing catalogue by chemical signalling by bioactive small transcripts at low concentrations. The of Actinobacteria: tracing the evolutionary history Julian Davies as if most of ‘Big Pharma’ lost interest of near-complete genome sequences molecules. This was first made obvious signalling functions of many of these of an ancient phylum. Microbiol Mol Biol Rev 71, Microbiology and Immunology, UBC, 495–548. in antibiotics at the same time. The of pathogens. In the 1990s, the only by the discovery of quorum sensing compounds have been demonstrated in Vancouver, Canada; Email [email protected] Waksman, S.A. (1961). The role of antibiotics older antibiotics still worked in most new antibiotics to be introduced were interactions in which the signalling cross-kingdom interactions. in nature. Perspect Biol Med 4, 271–287. The future discovery of new cases and the enormous cost of new ‘rediscoveries’ from earlier times. The molecule concentration is determined Walsh, C.T. & Fischbach, M.A. (2010). antibiotics and other therapeutic agents See Julian present his SGM Prize Medal antibiotic discovery and arduous clinical prospects for antibiotic discovery by the size of the bacterial population. Lecture ‘Molecules, Microbes and Me’ on Natural products version 2.0. J Am Chem Soc 132, can now be envisaged as a process trial procedures discouraged new were not promising. Quorum sensing has been identified in 26 March 2012 at the Society for General 2469–2493. involving the identification of biosynthetic investment when the long-term and The event that has brought about a many bacterial interactions. As mentioned Microbiology’s Spring Conference 2012 in Yim, G., Wang, H.H. & Davies, J. (2007). profitable illnesses of an aging population major philosophical change in antibiotic above, most bacterial genomes possess pathways for small molecules, and Dublin at http://bit.ly/Rg75WB Antibiotics as signalling molecules. Phil Trans needed attention. Production was even discovery was the complete genome biosynthetic pathways for a large number productive expression of the pathways R Soc B 362, 1195–1200.

202 Microbiology Today Nov 2012 Microbiology Today Nov 2012 203 Accessing the biosynthetic In an era of ever-increasing

antibiotic potential of resistance, can bacteria still Actinobacteria provide a source of desperately

needed novel Paul A. Hoskisson antimicrobials?

Secondary metabolite droplet on a The emergence of antibiotic- is not the only genus that is useful golden age of antibiotic discovery in power of whole-genome sequencing. is the biosynthetic potential of these Streptomyces lawn. Marco Gottelt (Groningen) resistant micro-organisms was inevitable industrially; indeed, many members of the 1960s, yet began to decline in the The emergence of rapid, next-generation organisms. We have known for many & Eriko Takano (Manchester) as soon as antibiotics were introduced to the phylum produce molecules that are 1970s and 1980s. This decline in the and third-generation sequencing years that most Streptomyces produce the vast array of drugs and treatments useful as antibiotics, anticancer agents, introduction of new antibiotics was technologies (454, Illumina, PacBio more than one secondary metabolite; available to clinicians. Perhaps one antihelminthics or immunomodulators; partly due to the rediscovery of the same and Ion Torrent) has further advanced however, studying the genome sequences surprise was the speed in which the these are often referred to as secondary molecules repeatedly in the same niches this progress at a pace, enabling rapid has shown us that these organisms have first cases of resistance were observed metabolites as they are not essential for (Actinobacteria are common inhabitants of and cost-effective genome sequencing the potential to produce many more, in pathogens. Soon after, the race to growth. soil), and partly through the tightening on the bench of any molecular biology potentially useful metabolites. The find new antibiotics began in earnest. The discovery, by Selman Waksman, of drug-licensing regulations, making it laboratory. The first completeStreptomyces model species, Streptomyces coelicolor A3(2), One source of potential new antibiotics that the Actinobacteria were a good source harder to bring new drugs to the market. genome was published in 2002, through was known to produce three secondary was the Actinobacteria, one of the most of secondary metabolites, through the However, with the need for new anti- a collaboration between Professor Sir metabolites – examining the genome abundant bacterial phyla on the planet, discovery of streptomycin production infective drugs probably greater than ever, David Hopwood’s group at the John sequence raised this number to over 20! comprising up to 30% of the bacterial by Streptomyces griseus in 1943, meant we need to be more cunning in our ability Innes Centre and the Wellcome Sanger This potential biosynthetic capability has flora in some niches. Within their ranks that this group subsequently received to discover and bring new antibiotics to Centre. Thereafter, the floodgates opened been a recurring theme as each genome are important human pathogens such an enormous amount of attention in the clinic. and there are over 100 Streptomyces sequence is completed and the sequence- as Mycobacterium tuberculosis, the causative order to add to our armoury of drugs. genome projects listed currently on gazing begins. They are often referred to agent of tuberculosis, but also the This arms race to find new weapons The power of sequencing GOLD (www.genomesonline.org). as silent gene clusters (the genes encoding important antibiotic producers such against resistant pathogens continued There are few, if any, areas of biology One of the most surprising findings to secondary metabolites are often found as the Streptomyces species. Streptomyces from the mid-1940s, through the that have remained untouched by the emerge from all these genome sequences together in clusters in the genome) as the

204 Microbiology Today Nov 2012 Microbiology Today Nov 2012 205 products have yet to be ‘seen’ in cultures to clone these genes from environmental There are limitations during biosynthesis, resulting in longer in molecular biology such as assembly gene cluster in the not-too-distant and are probably not expressed under the samples is now a real possibility, often or shorter chains, or without additional of large DNA fragments, ligation-free future. The assembly could be culture conditions that have been studied. referred to as the metagenomic approach. “to the modifications chemical decorations. Interestingly, one cloning, and the advent of ‘BioBrick’ undertaken using BioBrick-type This allows us to access novel secondary approach that has yielded amazing results technology (www.biobricks.org) to create technology where each genetic unit Giving a voice to the silent metabolites directly from the environment, that certain chemical is the formation of hybrid polyketides a truly synthetic biology for antibiotics. is pieced together like LEGO bricks until majority without the need to culture the producing simply by transferring polyketide clusters The multitude of secondary metabolite a complete cluster is assembled. There These previously unknown secondary organism. These genes can then be scaffolds are amenable into organisms producing related biosynthetic clusters available in the is still a lot of work to undertake, as metabolite gene clusters provide us with expressed in a suitable heterologous host molecules. This allows the machinery sequence databases means that we can with any synthetic biology project. a challenge – to activate them and study bacterial strain, of which there are many, to; however, we can from one cluster to modify the product assemble any enzyme simply from short We need to understand and develop the potential utility of their products. A including specially engineered strains of in another in a very simple manner (see oligonucleotides, introduce it into any good regulatory sequences and range of approaches has been taken to Streptomyces that don’t produce the majority envisage the very first, Fig. 1). biosynthetic cluster and examine the promoters, and efficient ribosome- study these clusters, including cloning of their own natural metabolites, and so potential to alter the characteristics of binding sites for manipulating expression them and expressing them in another are excellent producers of heterologous truly synthetic antibiotic Towards a truly synthetic the metabolite produced. levels and the overall logistics of Streptomyces species. This may enable the metabolites. One of the keys to identifying biology of antibiotics Of course, there are limitations piecing these together. Yet all of these global regulatory processes controlling clusters using this approach is to explore biosynthetic gene The relatively simple experiments that to the modifications that certain chemical approaches are tantalisingly within our their expression in their native producer previously neglected environmental have been carried out to date have scaffolds are amenable to; however, grasp and will enable us to carry out to be circumvented. Simple disruption niches, such as the deep-sea environment, cluster in the not- wide-ranging implications; however, now we can envisage the very first, truly bio-inspired chemistry synthetically in of the pathway-specific regulators, which hyper-arid deserts and Antarctica, all of we can couple these with the advances synthetic antibiotic biosynthetic a bacterium in the near future. are easily identified within secondary which are yielding potentially interesting too-distant future. metabolite clusters by bioinformatics, has new antibiotics. The limitation of these OH O Me N(Me) Acknowledgements so-called ‘non-natural natural” products’ 2 H Thanks to Professor Sir David Hopwood for the been shown to result in activation of the approaches is the intensive screening using an approach called combinatorial HO OH O Me O H genes within a cluster. Other approaches required to identify biological activity in biosynthesis (using genetic engineering H use of the picture in Fig. 1. COOH Me O O have included the manipulation of the cloned sequences. to modify biosynthetic pathways to H OH O 2 Paul A. Hoskisson antibiotic genes through the use of make new compounds). The ability to H O O O Strathclyde Institute of Pharmacy & Biomedical short DNA sequences that interfere with Synthetic biology manipulate these clusters using molecular regulatory proteins, thus ameliorating approaches to new Actinorhodin Medermycin Sciences, University of Strathclyde, 161 Cathedral biology offers several advantages, not only (S. coelicolor) the effects of proteins that repress gene antibiotics (S. AM-7161) Street, Glasgow G4 0RE; Tel. +44 (0)141 548 in terms of generating novel activities, 2819; Email [email protected] expression. The use of various stress and One of the most exciting approaches but also improving the pharmacokinetics nutritional conditions has also yielded to emerge recently is the potential to of drugs, and reducing toxicity. Further reading good results in terms of manipulating apply synthetic biology to antibiotic One group of secondary metabolites Medema, M.H., Breitling, R., antibiotic production, such as the use production, discovery and manipulation. that has been amenable to combinatorial Bovenberg, R. & Takano, E. (2010). of common soil carbon sources such Synthetic biology can be thought of as biosynthesis and has received lots of Exploiting plug-and-play synthetic biology N(Me)2 as N-acetylglucosamine to activate the repurposing or redesign of biological for drug discovery and production in attention is the polyketides. Polyketides HO OH O Me expression of previously unobserved systems for novel applications. The are synthesised by large multimodular Mederhodin H microorganisms. Nat Rev Microbiol 9, (First ‘hybrid’ metabolites. This enhancing of secondary clustering of secondary metabolite Me O O 131–137. enzymes that link simple precursors, antibiotic 1985) H metabolism through the manipulation of genes offers a big advantage to the such as acetyl-CoA or malonyl-CoA, in Hiang, Y.-M., Chang, S.-L., Oakley, B.R. H & Wang, C.C. (2011). Recent advances in cellular metabolism has great potential manipulation of their function, an iterative nature, growing chains that OH O O O awakening silent biosynthetic gene clusters and for awakening these silent clusters. expression levels and production. are tethered to an acyl carrier module linking orphan clusters to natural products in Recently there have been significant Whilst synthetic biology is one of the on the enzyme. Manipulation of these microorganisms. Curr Opin Chem Biol 15, advances in the cloning of large DNA current ‘buzz’ words in biology, this Fig. 1. Hybrid polyketide biosynthesis. Streptomyces sp. AM-7161, making the brown- multimodular enzymes then allows 137–143. fragments directly from the environment. manipulation of antibiotic biosynthetic pigmented medermycin (top right) and S. coelicolor making the blue-pigmented for alteration of the metabolite chain. Winter, J.M., Behnken, S. & Hertweck, C. The gene clusters that encode secondary actinorhodin (top left). The actinorhodin biosynthetic cluster was introduced into clusters is not particularly new. Since the Several methods have been used, such as (2011). Genomics-inspired discovery of natural Streptomyces sp. AM-7161, creating the hybrid polyketide, which was called mederrhodin metabolites are generally in the region of mid-1980s, various groups interested those where simple gene disruptions products. Curr Opin Chem Biol 15, 22–31. 25–60 kbp in length; therefore, the ability in Streptomyces have been trying to make can alter one of the chemical reactions (bottom), which differed from medermycin in the addition of an -OH group. David Hopwood

206 Microbiology Today Nov 2012 Microbiology Today Nov 2012 207 Waging war on Neil A.R. Gow fungi – the Gordon D. Brown unknown Alistair J.P. Brown Mihai G. Netea superbugs Karen E. McArdle

Despite the alarming number The public have come to impressive. Let’s consider some more incidence rates than superficial infections recognise infectious diseases caused by statistics and fungal factoids. Fungal but have alarmingly high mortality rates, bacteria such as MRSA, C. difficile, E. skin, hair and nail infections are an despite treatment with antifungal drugs. of people (not to mention coli and Legionella, viruses (e.g. common itch that affects a quarter of the world’s Patients with compromised immune cold, influenza, AIDS) and parasites (e.g. population. These common infections are systems (associated with cancer, trauma crops and animals) killed malaria, leishmaniasis, sleeping sickness) caused by dermatophytes and give rise and HIV) and those undergoing invasive as household names, while those caused to several well-known conditions, such as clinical procedures (stem cell, bone by serious fungal infections by fungal pathogens such as Candida, athlete’s foot (tinea pedis) and ringworm and organ transplants) are particularly Aspergillus, Cryptococcus, Pneumocystis and of the scalp (tinea capitis). Mucosal susceptible to these invasive, life- every year, funding for others, remain unknown, unfeared infections of the mouth and genitals threatening infections, and mortality and often undiagnosed. However, are also common. For example, it rates mostly range from 30 to 80% medical mycology research each year fungi are responsible for is estimated that 75 million women depending on the invading pathogen around 1.5 million deaths and cost $12 experience recurrent episodes of and the underlying condition. Current billion to treat worldwide. In addition, vulvovaginal candidiasis (or thrush) figures for incidence and mortality rates is disproportionately low. fungal pandemics threaten ecologically annually. Oral thrush is more likely to are likely to be underestimated due important groups of animals and staple occur in babies, denture wearers and to inadequate epidemiological data, However, the researchers are crops in a way that threatens global individuals using inhaled corticosteroids misdiagnosis because of unreliable biodiversity and food security. Why is it, for asthma. Fungal allergy is also diagnostics and a lack of global reporting starting to fight back … therefore, that so little emphasis is placed common, but robust epidemiological in areas of the world with high endemic on fungal pathogenicity in general, and statistics elude us. Although disease problems. Incredibly, only one in particular, only about 2–3% of the uncomfortable and distressing to the fungal disease (coccidioidomycosis) The Fungus, by Harry Adam Knight infectious disease research budget is individual, these infections and allergies holds the status of a notifiable disease (published by Star Books), speculates currently devoted to medical mycology in are not often life-threatening and are at the Centers for Disease Control and on the fictitious ravages of medical the UK, USA and Europe? generally treatable. Prevention (USA). mycology. Used by permission of The Random The reason is clearly not due to Of greater concern are invasive While there are over 600 species of House Group Ltd size of the clinical burden – which is fungal infections which have much lower fungi that can infect humans to cause

208 Microbiology Today Nov 2012 Microbiology Today Nov 2012 209 It is barely a variety of diseases, over 90% of all for more deaths than malaria and AIDS- individuals. It is the number one most awarded a £5 million Strategic Award well as a limited number of postdoctoral fungus-related deaths are due to species associated tuberculosis. serious infection in people with advanced (WTSA) to the University of Aberdeen fellowships. Invitations for projects for “ belonging to only four genera; Candida, Aspergillus-related infections mainly HIV. Calculations using existing data to lead a major pan-UK consortium these posts are available to academic appreciated that the Cryptococcus, Aspergillus and Pneumocystis. arise in the lungs (e.g. chronic obstructive estimate that the worldwide incidence of in Medical Mycology and Fungal and clinical staff at any UK university. Candida species are the fourth most aspergillosis) and can be life-threatening Pneumocystis infection is at least 400,000 Immunology, which will tackle some of (For information about the funding burden of cryptococcal common cause of hospital-derived to individuals with underlying conditions cases every year with mortality rates the major problems in this important but opportunities supported through this bloodstream infections in the developed like tuberculosis, chronic obstructive varying between 20 and 80%. neglected field of medicine. This pan-UK WTSA, please see www.abdn.ac.uk/ disease in sub-Saharan world. The estimated annual global pulmonary disease (COPD) and cystic Regardless of the global health consortium has three objectives: (i) to mmfi) incidence of candidiasis, a bloodstream fibrosis. Current estimates for invasive and economic burden, fungal diseases provide training for a new generation of Mycologists have begun to fight Africa is so high that infection caused by Candida albicans, is aspergillosis show greater than 200,000 remain understudied and they remain medical mycologists in areas of the world back, but the war has only just begun. 400,000 cases per year. Approximated cases per year worldwide and there the unknown superbugs. There is a with high endemic diseases and little High-quality research around the world it accounts for more mortality rates for candidiasis are very may be a further 450,000 deaths per clear need now to seriously advance specialist expertise; (ii) to build clinical is beginning to make inroads to these high, ranging between 46 and 75%. annum due to COPD. Despite early our understanding of fungal infection academic capacity in the UK; and (iii) terrible human diseases, and initiatives deaths than malaria There are over one million cases of diagnosis and treatment, this invasive and immunity. Other issues that require to foster and promote cross-disciplinary like the WTSA are enabling the linking Cryptococcus infections per year worldwide. disease carries an overall 50% mortality urgent attention include the need to invest research excellence that takes advantage of arms and assembly of forces for The majority of cases present with rate and, if undiagnosed, the outcome in the development of safer and more of the highly active, but dispersed a coordinated attack on a too-long and AIDS-associated meningoencephalitis (meningitis). AIDS is almost certainly fatal. In addition, effective antifungal drugs and fast, reliable communities of medical mycologists in neglected group of pathogens. patients are particularly susceptible and Aspergillus fumigatus is also classified as diagnostics. Again, it is salutary that, in the UK. The focus of the research will be tuberculosis. mortality rates among this group vary an aeroallergen and is linked to the terms of preventing fungal infections, to promote studies that will develop new Neil A.R. Gow ” significantly, depending on geographical development of severe asthma with there are currently no approved human chemotherapies, immunotherapies and Gordon D. Brown location, with 15–20% in the USA and fungal sensitisation (SAFS), which is vaccines for any fungal pathogen, and this diagnostics through an understanding of Alistair J.P. Brown 55–70% in sub-Saharan Africa and Latin thought to affect up to 13 million adults situation needs immediate attention. fundamental aspects of medical mycology Mihai G. Netea† America. It is barely appreciated that the worldwide. In response to a call for urgent action and fungal immunology. The resources Karen E. McArdle burden of cryptococcal disease in sub- Pneumocystis gives rise to pneumonia- to redress the balance in infectious disease that have been funded will support basic Aberdeen Fungal Group & Wellcome Trust Saharan Africa is so high that it accounts like symptoms in immunocompromised research, the Wellcome Trust has recently science and clinical PhD studentships as Strategic Award in Medical Mycology and Fungal Immunology, Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD; Tel. +44 (0)1224 438473; Email [email protected] († Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands).

Further reading Brown, G.D., Denning, D.W, Gow, N.A.R., Candida albicans Levitz S.V. Netea, M.G. & White, T.C. (left, SEM), (2012). Human fungal infections: the hidden Aspergillus fumigatus killers. Science Translational Medicine (in press). (centre, SEM) Brown, G.D., Denning, D.W & Levitz and Cryptococcus S.V. (with Gow, N., Netea, M. & White, neoformans (right, T.). (2012). Tackling human infections. Science India ink stain) – (Editorial) 336, 647. three of the four Fisher, M.C., Henk, D.A., Briggs, C.J., biggest fungal killers Brownstein, J.S., Madoff, L.C., McCraw, worldwide. N. Gow (C.a.) S.L. & Gurr, S.A. (2012). Emerging fungal Eye of Science / Science Photo threats to animal, plant and ecosystem health. Library (A.f.) – CDC/ Nature 484, 186–194. Dr Leanor Haley (C.n.)

210 Microbiology Today Nov 2012 Microbiology Today Nov 2012 211 Enzybiotics and phages: safe alternatives to antibiotics in the control of food safety

The concept of treating bacterial infections with phage is not new – indeed it pre-dates the antibiotic era. Can this be used to eliminate the use of antibiotics in animal feed?

Recently, the US Food & Drug ANTIBIOTIC RESISTANCE furazolidone, nitrofurazone and Administration (FDA) issued an order The FDA is concerned about the sulfonamide derivatives, formerly used Patricia Veiga-Crespo & Tomas G. Villa prohibiting the use of cephalosporin use of antibiotics in food-producing in the treatment of lactating cattle. drugs in cattle, swine, chickens and livestock because they are likely to Bacterial antibiotic resistance can be turkeys (docket no. FDA-2008-N-0326; contribute to the generation of resistant acquired by two mechanisms: (i) as the www.regulations.gov). Cephalosporin- strains of certain bacterial pathogens, result of genetic events causing variations based antibiotics are important in treating thus increasing the risk of antibiotic- in the bacterial genome; or (ii) by human diseases such as pneumonia resistant infections in humans. In horizontal gene transfer among bacteria. caused by Streptococcus pneumoniae, or the case of cephalosporins, the risk The fight against antimicrobial skin and soft-tissue infections caused of microbiological or toxicological resistance has become a great challenge by Staphylococcus aureus and Streptococcus undesirable side effects in food-producing to our civilisation and involves a wide pyogenes. These drugs are also effective animals still remains unknown. But it is range of experts from different echelons against other bacteria, such as Acinetobacter generally assumed that adding antibiotics of society and from all over the world. calcoaceticus, Bacteroides fragilis, Enterobacter to animal food in order to increase food In agriculture, for example, the FDA, via agglomerans, Escherichia coli, Haemophilus production may threaten public health the National Antimicrobial Resistance influenzae (including β-lactamase- and should be discontinued. When the Monitoring System (NARMS), is charged producing strains), Klebsiella oxytoca, cephalosporin prohibition finally takes with the responsibility of investigating Klebsiella pneumoniae and Pseudomonas effect, the drug will join others, such resistance trends in food-borne bacteria, aeruginosa. as chloramphenicol, dimetridazole, assessing antimicrobial resistance risks for Chickens on a fence. Digital Vision / Thinkstock

212 Microbiology Today Nov 2012 Microbiology Today Nov 2012 213 As for the undesirable” side effects of enzybiotics, they have been scarcely reported, and

new antimicrobial drugs, and promoting they have the reduced the interest in bacteriophages of using bacteriophages as biocontrol of phage-lytic enzymes known as Delfini, C., Cersosimo, M., Del Prete, the judicious use of medically important additional as therapeutics. But the increase in agents to reduce Salmonella in poultry enzybiotics. In fact, the term enzybiotic V., Strano, M., Gaetano, G., Pagliara, antimicrobials approved for use in food- antibiotic resistance has now resulted in a products has been well documented. is a wider term that refers to those A. & Ambro, S. (2004). Resistance producing animals. advantage resurgence of interest in bacteriophages. Phages have also been proposed as enzymes, independent of their origin, screening essay of wine lactic acid bacteria The increase in antimicrobial The potential of bacteriophages as alternatives to antibiotic sprays to control that are able to act as antibacterial or on lysozyme: efficacy of lysozyme in that their unclarified grape musts. J Agric Food Chem resistance rates seen during the last therapeutic agents was first evaluated in bacterial infections in high-value crops. antifungal agents. 52, 1861–1866. few decades is likely to be the result immunogenic fields such as aquaculture, biocontrol in Advances in molecular biology They are used as food additives Huff, W.E., Huff, G.R., Rath, N.C., of misuse and overuse of antibiotics; agriculture and in veterinary medicine. have allowed researchers to focus on two and preservatives, for example in the abilities are Balog, J.M. & Donoghue, A.M. (2005). new resistant bacterial strains have The success of phage therapy for the main aspects of bacteriophage-based production of cheese and wine; in Alternative to antibiotics – utilization of emerged and, therefore, the battery of quite weak. treatment of septicaemia and meningitis therapies: (i) administration of whole medical applications, such as eye drops; bacteriophage to treat colibacillosis and chemotherapeutical drugs available to ” in chickens and calves, or the possibility bacteriophages; and (ii) administration and in toothpaste, etc. The FDA has prevent food-borne pathogens. Poult Sci 84, treat disease has dwindled. This has approved the use of bacteriophages to 655–659 resulted in an enormous worldwide health control Listeria monocytogenes in cheese, Kreling, D.H., Mott, D.A., Wiederholt, care problem, in terms of declining public thus classifying them as ‘GRAS’ J.B., Lundy, J. & Levitt, L. (2001). health and spiralling health care costs. (generally recognised as safe) in 2006 Prescription Drug Trends. A Chart-book Update. The World Health Organization (WHO) (notice no. GRN 000198; www.fda.gov). Menlo Park, CA: The Henry J. Kaiser Family Foundation. defined the appropriate use of antibiotics Additionally, in 2007, the status of GRAS Leverentz, B., Conway, W.S., as ‘the cost-effective use of antibiotics, which was extended to bacteriophage use on all Janisiewicz, W. & Camp, M.J. (2004). maximizes clinical therapeutic effect while food products (notice no. GRN 000218; Optimizing concentration and timing of a minimizing both drug-related toxicity and the www.fda.gov). phage spray application to reduce Listeria development of antibiotic resistance’. As for any undesirable side effects monocytogenes on fruit tissue. J Food Prot 67, Changes within the pharmaceutical of enzybiotics, they have been scarcely 1682–1686. industry may be contributing to the pipeline reported, and they have the additional Talbot, G.H., Bradley, J., Edwards, J.E., of new antimicrobials drying up; in fact, advantage that their immunogenic Gilbert, D., Scheld, M. & Bartlett, J.G. the major pharmaceutical companies have properties are weak. Despite the fact (2006). Bad bugs need drugs: an update practically stopped research leading to that further investigation on the methods on the development pipeline from the the development of new antibiotic drugs. for their administration, half-life and Antimicrobial Availability Task Force of the Infectious Diseases Society of America. Clin One of the reasons for this cessation is the effectiveness is still required, enzybiotics Infect Dis 42, 657–668. reduced market profits for antimicrobials, constitute a clear and safe alternative to Touch, V., Hayakawa, S., Fukada, K., as compared to those generated by other antibiotics as food control agents. Aratani, Y. & Sun, Y. (2003). Preparation drugs, such as those targeting chronic of antimicrobial reduced lysozyme Patricia Veiga-Crespo diseases. In 2000, amoxicillin-clavulanic compatible in food applications. J Agric Food Microbiology Area, Dept of Chemistry, Faculty acid was the only antibiotic in the top 20 Chem 51, 5154–5161. of Sciences, University of Burgos, Spain; Email prescription drugs. Therefore, the situation Veiga-Crespo, P., Ageitos, J.M., Poza, [email protected] needs to be addressed. M. & Villa, T.G. (2007). Enzybiotics: a look Tomas G. Villa to the future, recalling the past. J Pharm Sci BACTERIOPHAGE Dept of Microbiology and Parasitology, 96, 1917–1924. Bacteriophages are the most abundant Faculty of Pharmacy, University of Santiago WHO (2001). WHO Global Strategy for Containment of Antimicrobial Resistance. www. and diverse biological agents on the planet de Compostela, Spain; Email tomas.gonzalez@ who.int/csr/resources/publications/ and have been detected in virtually all usc.es drugresist/WHO_CDS_CSR_ environments. They were discovered in the DRS_2001_2_EN/en/ early 20th Century and have been applied Further reading in the control of bacterial diseases. Barrow, P., Lowell, M. & Berchieri, A. However, the discovery of antibiotics (1998). Clin Diagn Lab Immunol 5, 294–298.

Bacteriophage virions. Eye of Science / Science Photo Library

214 Microbiology Today Nov 2012 Microbiology Today Nov 2012 215 It isn’t just soil-dwelling actinomycetes that may hold the key to new antimicrobial compounds. Insect-pathogenic bacteria also produce a host of bioactive compounds – and what’s more, they are easy to analyse in vivo.

Natural products from microbes and plants This dramatic situation in the clinic contrasts Photorhabdus and GameXPeptide A, a have been used in human medicine for thousands of with the enormous possibilities of modern science. Xenorhabdus are potent cyclic pentapeptide from years. During the last 60 years they have been especially Next-generation sequencing allows cheap and rapid natural-product- Photorhabdus useful as antibiotics and anti-cancer compounds. Most access to biosynthesis gene clusters in bacteria and producers low-molecular-mass compounds used clinically are in fungi, which can be manipulated very efficiently in Detailed analysis of well-known fact natural products, natural product derivatives or have the original host using genetic tools, or expressed antibiotic producers like Streptomyces Isopropylstilbene from been inspired by natural products. However, the current heterologously in more accessible model organisms, has shown that their potential to Photorhabdus required situation where we have antibiotics to treat many bacterial such as Escherichia coli, Bacillus or optimised Streptomyces produce novel compounds is still for Heterorhabditis infections is likely to change rapidly in the next decade or hosts. Additionally, analytical methods, like mass enormous. In addition, it has been development. Photorhabdus is the only two due to increasing resistance and the emergence of not spectrometry, allow the rapid detection and structural shown over the last few years that non-plant organism able only multi-, but pan-resistant human pathogens. At the elucidation of novel natural products or their several other bacterial phyla are in fact to produce stilbenes. same time, pharmaceutical companies have stepped back derivatives. The development of these tools has already promising natural-product-producers. from antibiotic research due to high development costs and led to the revitalisation of academic natural product Five years ago, we started to analyse have concentrated mostly on drugs for chronic diseases. research. bacteria of the genera Photorhabdus Prexenocoumacin C from and Xenorhabdus for their ability to Xenorhabdus nematophila. produce natural products, as earlier Prexenocoumacins are inactive prodrugs of work had revealed the presence of Helge B. Bode the potent antibiotic compound classes unique to these xenocoumacin-1, which Drugs bacteria. Photorhabdus and Xenorhabdus result from cleavage by a belong to the Enterobacteriaceae and live in specific peptidase. symbiosis with nematodes of the genera Heterorhabditis and Steinernema, respectively. Both bacterium and nematode form an entomopathogenic complex that can from Rhabduscin produced infect and kill several soil-dwelling insect by Xenorhabdus and larvae and therefore this complex can Photorhabdus that inhibits be used industrially for pest control in phenoloxidase, which organic farming. The nematode can be is part of the insect regarded as the carrier for the bacteria, immune system. bugs setting them free once inside the insect, and the bacteria essentially function as the warhead that kills the insects. Several protein toxins are major players in carrying out their deadly job; there that are also a number of low-molecular- mass natural products with insecticidal activity that have also been isolated from these bacteria. Another peculiarity of Photorhabdus is its bioluminescence, kill which makes it unique among terrestrial Xenematide bacteria, and it is already an established from Xenorhabdus tool in modern molecular biology, nematophila, an insecticidal although its true biological function is depsipeptide. still not understood. bugs H.B. Bode

216 Microbiology Today Nov 2012 Microbiology Today Nov 2012 217 The high degree of” bioactive compounds in general may be the result of the specific ecological niche these bacteria inhabit.” not understood, these promoters have been exchanged of their possible interaction partners in their natural with strong constitutive or inducible promoters, enabling environment, the soil. Photorhabdus and Xenorhabdus can be ‘on demand’ and high-titre production of selected grown in the lab alone or together with their interaction compounds. With the genomes of several chemically partners (nematodes, insects or food competitors), diverse strains in hand and several biosynthesis gene allowing the analysis of all possible growth phases of clusters responsible for the production of typical natural these bacteria using analytical and molecular biology products like peptides and polyketides already identified, methods. It is evident that some of these natural products the promoter exchange approach can now be applied to must play an important role in mediating these complex several strains. interactions from their conservation in several distantly The high degree of bioactive compounds in general related bacterial strains. may be the result of the specific ecological niche these In summary, GameXP has placed Xenorhabdus bacteria inhabit. Being nematode symbionts they must and Photorhabdus in the company of other well-known be able to switch between a mutualistic (towards the natural-product-producers like Streptomyces, Bacillus nematode host) and a pathogenic (towards the insect and myxobacteria. Although their compounds still prey) growth phase; this may require the production have much to prove in terms of potency as clinical Top left Larvae of the Greater waxmoth (Galleria of specific small-molecule effectors, signals or toxins. antibiotics or anti-cancer compounds, their potential for mellonella) infected with Photorhabdus showing the typical bioluminescence. G. mellonella is used as Additionally, they have to protect the dead insect from therapeutic use is very high. a model for bacterial infections. H.B. Bode food competitors, such as soil-dwelling bacteria, fungi and amoebae. Thus, the biochemical similarity between Acknowledgements Bottom left Tobacco hornworm (Manduca sexta) caterpillar amoeba and human parasites, such as Plasmodium, may The author is grateful to the GameXP team and all members of used as a model for bacterial infections. H.B. Bode be the reason for the bioactivities observed. his group for their enthusiasm and fun during recent years. The Top right Inhibition zones of compounds from One major question is how do the bacteria know work was supported by the EC’s Seventh Framework Programme Xenorhabdus against Micrococcus luteus. H.B. Bode where they are and what compounds are to be produced (FP7/2007-2013) under grant agreement no. 223328, the German Research Council (DFG) and the LOEWE excellence program in their given environment? The group of Jon Clardy Bottom right Inhibition zones of compounds from Insect Biotechnology. Xenorhabdus against E. coli. H.B. Bode in Harvard has shown that insect blood might trigger the production of some (insecticidal?) natural products. Helge B. Bode Further triggers are likely to be discovered in the future Merck Stiftungsprofessur für Molekulare Biotechnologie, During the course of the EC-funded project from simple amino acid derivatives like phenylalanine- as these bacteria contain a variety of different sensor Fachbereich Biowissenschaften, Goethe Universität Frankfurt ‘Genomic approaches to metabolite exploitation from derived cinnamic acid or simple amides to very large systems that might be involved in integrating different Max-von-Laue-Str. 9, 60438 Frankfurt am Main, Germany; Xenorhabdus/Photorhabdus’ (GameXP) with partners peptides with a molecular mass greater than 1,800 Da. environmental cues. Tel. +49 69 798 29557; Email [email protected] from the UK (Sharon Peacock, Cambridge; Nick All compounds have been tested against different insects Waterfield, Bath; Richard ffrench-Constant, Exeter), or insect cells, pathogenic bacteria and parasites such as Finding the true Further Reading Thailand (Narisara Chantratita, Bangkok), Vietnam Leishmania (leishmaniasis), Trypanosoma (sleeping sickness function of natural products Bode, H.B. (2009). Entomopathogenic bacteria as source of new (Long Phan Ke, Hanoi) and Germany (Vera Siegmund, and Chagas disease) or Plasmodium (malaria). Different Another advantage of these bacteria is that the real secondary metabolites. Curr Opin Chem Biol 13, 224–230. Saarbrücken), the chemical diversity of these bacteria insecticidal and antibiotic compounds have been function of natural products can be studied. Although Crawford, J.M. & Clardy, J. (2011). Bacterial symbionts and natural products. Chem Comm 47, 7559–7566. was investigated and exploited. More than 200 different identified and, more surprisingly, a high proportion of natural products are indeed important therapeutics, the Chaston, J.M., Suen, G., Tucker, S.L. & others (2011). The bacterial strains were isolated from nematode-infected compounds showed activity against the human parasites function and regulation mechanisms leading to their entomopathogenic bacterial endosymbionts Xenorhabdus and insects obtained from soil samples (some together with tested, and some of these are being analysed in detail production are mostly unknown. It is clear that bacteria Photorhabdus: convergent lifestyles from divergent genomes. PLoS their associated nematodes) and the bacterial strains were using in vivo models. in general do not produce these compounds for the One 2011 6, e27909. analysed using mass spectrometry. Using bioinformatics, Another goal of GameXP was to improve the purpose of selling them in a pharmacy! To analyse the Reimer, D., Pos, K.M., Thines, M., Grün, P. & Bode, H.B. over 500 novel compounds have been identified in these production of these bioactive compounds and to increase natural function of compounds in established producers (2011). A natural prodrug activation mechanism in nonribosomal bacteria and more than 150 compounds have been the chemical diversity. As the regulation of the promoters such as Streptomyces or Bacillus is more challenging than peptide synthesis. Nat Chem Biol 7, 888–890. isolated and/or synthesised. These compounds range that drive the expression of these compounds is often in Photorhabdus or Xenorhabdus, as we know only a fraction

218 Microbiology Today Nov 2012 Microbiology Today Nov 2012 219 schoolZone

Antibiotics in action

Virtually everybody at some point in their life has been in the lab, and the clinic, is an artefact Saccharopolyspora and Micromonospora as phosphorylation, glycosylation, the antibiotic course even when you of using such antibiotics at higher producing a multitude of clinically adenylation, degradation), altering are feeling better, and practice good prescribed antibiotics by their doctor. These drugs form one concentrations than they would occur important antibiotics. Another group the target of the antibiotic (such as basic hygiene such as washing your of our mainstays in health care against infectious diseases in nature. That said, they are very useful of bacteria, the myxococci have more altering ribosomes, remodelling their hands regularly and covering your nose along with vaccination. Interestingly, almost all of these drugs for human health and it is a good thing recently revealed themselves as a good cell wall) so the antibiotic cannot bind and mouth with a tissue whenever you that they affect biological processes this source of potentially useful antibiotics. to its target, or by efflux, essentially sneeze or cough. These are very simple are natural products made by micro-organisms to help them way! In fact it has been estimated that Generally the micro-organisms that ejecting the compound from the cell. but effective ways of stopping the spread compete in the natural environment. Here, we try to answer the introduction of antibiotics led to an are prolific producers tend to come Many of these mechanisms are used by of resistance and infectious diseases. 8-year increase in human life expectancy. from highly competitive environments the producing bacteria to avoid suicide The discovery of the first natural some of the most common questions regarding antibiotics. where they may interact with a range and they become important when the product antibiotic, penicillin, in 1928 What are antibiotics? that they were produced as chemical What kinds of micro-organism of other organisms. Soil has traditionally same resistance arises in pathogenic triggered a golden age of antibiotic Antibiotics are usually small chemical weapons to kill competitor micro- make antibiotics? been a good hunting ground for finding bacteria. This can arise through discovery that revolutionised medicine. molecules that micro-organisms make organisms and provide an evolutionary Many different types of micro-organism antibiotic-producing micro-organisms, spontaneous mutations (a minor route) In addition to treating infections and secrete into the environment advantage in highly competitive can produce antibiotics – indeed many and this has been extended recently to but more commonly by horizontal and cancers, natural products have where they can have an effect on other environments such as soil. This view species make several different secondary looking in unusual soils from extreme gene transfer, a process whereby revolutionised surgery and made organ organisms. Antibiotics belong to many is changing and it is clear that many metabolites depending on the growth environments such as from permafrost pathogens can acquire resistance genes transplantation possible. Despite this, different chemical classes and have a compounds only have antibiotic activity conditions or at a different stage of areas and hyper-arid soils from deserts. from antibiotic-producing bacteria in very few new antibiotics have made wide range of targets within the cell. at relatively (and artificially) high their lifecycle. The majority of antibiotics Deep-sea marine sediment has yielded the environment. A good example is it to the clinic since the 1980s and, They range from small-molecular- concentrations. It is these high levels that used in medicine are natural products many interesting compounds in recent vancomycin that is used as the drug with multidrug-resistant infections on mass compounds such as the phenolic are used in the clinic to treat infections, that are made by large-scale industrial years, with one actinobacterium, of last resort for treating meticillin- the increase, we are fast approaching antibiotic chloramphenicol, which is but in the natural environment they are fermentation processes. The best-known Salinispora, producing several useful resistant Staphylococcus aureus (MRSA). a new age without antibiotics. This made by Streptomyces venezuelae, present at much lower concentrations antibiotic, and the first to be discovered, antibiotics and anti-cancer drugs. Vancomycin and related glycopeptide imminent crisis has spurred academics and still commonly used to treat eye and are likely to have signalling roles, is penicillin, made by the fungal genus antibiotics are made by actinobacteria and big pharmaceutical companies infections like conjunctivitis (although either within a species or across species. Penicillium and some of its relatives, Why do we see resistance? that live in the soil, but over a period into action, and with the advent of all the chloramphenicol used today is Interestingly, antibiotics fall into a but the undoubted kings of antibiotic Resistance to antibiotics is not really a of 45 years the five core resistance genome sequencing and many other chemically synthesised as it is cheaper wider group of molecules produced by production are bacteria. In particular, the surprise because bacteria that make genes have spread from Streptomyces technological advances since the so- than S. venezuelae fermentation), micro-organisms, named ‘secondary Actinobacteria (a large and abundant antibiotics have to be resistant to to MRSA to give vancomycin-resistant called golden age, the battle against through to the large macrolide metabolites’. They are so named bacterial phylum accounting for almost them to avoid killing themselves! The MRSA (VRSA), a new superbug resistant drug-resistant infections may just swing compound erythromycin made by because they are not essential (i.e. 30% of all bacterial species) with genera resistance genes encoded by antibiotic- to almost all known antibiotics. back in our favour. Natural products Saccharopolyspora erythraea, used to they are secondary) for growth of the such as Streptomyces, Amycolatopsis, producing bacteria can spread to remain our best hope of treating disease treat respiratory infections. Small peptide producing organism, and it may be that disease-causing bacteria How can we prevent the but we know that resistance is inevitable. antibiotics (e.g. colistins and lantibiotics) large-scale production is only observed under evolutionary spread of resistance? This means the battle will continue for as have come to prominence in the last under laboratory conditions. Moreover, selective pressures, e.g. We know that resistance to every long as humans survive because we will few years. In fact one lantibiotic, nisin, many of the organisms that produce exposing pathogenic antibiotic is present in the environment always need new antibiotics. is widely used as a food additive. antibiotics also produce other secondary bacteria to antibiotics. and can potentially be transferred from metabolites that affect the growth of There are lots of ways that one strain of bacterium to another. Matt Hutchings, University Why do micro-organisms other kinds of cells, such as cancer cells, micro-organisms can avoid However, we can significantly slow this of East Anglia, Lorena T. make them? or modulate the immune response, or being killed by antibiotics process down and avoid the spread of Fernández-Martínez, John Innes The exact function of antibiotics in the even kill fungi, parasites and worms. So and these include resistance simply by using antibiotics Centre & Paul A. Hoskisson, natural environment is a source of much with such a diversity of activities it seems altering the antibiotic to responsibly, i.e. use them exactly as University of Strathclyde debate. Traditional views have been most likely that the response we observe prevent its action (such prescribed by the doctor, always finish Antibiotics. Stockbyte / Thinkstock

220 Microbiology Today Nov 2012 Microbiology Today Nov 2012 221 A taste of honey

Ian Richardson & Annabel Large

The extended essay is an essential Initially, I was quite daunted by associate lecturer at Cardiff School of component of the International the ‘extended essay’; I had no idea what Health Sciences. Both replied in great Baccalaureate diploma course for topic to pursue, what was accessible or detail and right from the start they students studying at Rydal-Penrhos most appropriate. However, I was clear reassured me that it would be possible School in North Wales. Students have to that it was going to be a science-based to conduct an experiment to replicate decide on a subject and a specific area project. A BBC news article discussing some of their findings. They sent of interest early in the lower sixth. In honey also inspired me with its potential further articles, research papers and biology, they are encouraged to research to act as an antimicrobial agent to even discussed general methodology their chosen area and develop research counter hospital-acquired infections and appropriate microbes to use. They and practical skills. Both organisation like MRSA. This had me captivated to introduced me to the ‘Microbiology and planning are crucial, especially in think that a substance like honey could Twitter Journal Club’, which I logged a practical-based subject. They must be used to breakdown and weaken onto and received insightful findings learn to work within a department and a complex resistant strain of bacteria from other researchers. plan the use of resources and lab time. that has been troubling the medical As a result of this input my This is done under the watchful eye of profession for years. At this point I was research question was conceived, ‘Do a supervisor, who guides and provides a advised to contact the SGM, I wasn’t the antimicrobial properties of regional framework in the form of checkpoints expecting much feedback as a sixth honey differ to manuka honey and over the year to monitor progress. form student and did not think anyone how could these unique antimicrobial This year we were fortunate for would be that interested. But, I was properties be incorporated in modern one student to establish a link with absolutely taken aback by the response medicine in the fight against resistant the SGM that enabled us to utilise I received. The SGM team put me in strains of bacteria?’ The use of local their knowledge and resources – the contact with Jenny Hawkins at Cardiff honey was unique in my project link was established after a speculative University and Dr Sarah Maddocks, an because both centres had never tested phone call. The antimicrobial properties honey from North Wales. As a result of honey was at the heart of the of the collaboration I agreed to supply discussion after the student, Annabel the honey I tested to both research Large, had read various articles about establishments. manuka honey and its historical use as Throughout my investigation, I a treatment against bacterial infection. had continued support from these It was not long after this initial contact leading researchers and I would that Annabel was advised to contact strongly advise anyone to do the various University lecturers and the same. Although challenging at times, whole project suddenly burst into life. it has been an extremely worthwhile The whole experience has been very and exciting experience. I owe a great positive from a supervisor’s point of debt of thanks to the SGM staff and view and I am very grateful for the time Dr Maddocks and Jenny Hawkins in and effort the scientists have invested in Cardiff. I am happy to report the first Annabel’s project. draft is now written and I am well on the way to completing the task! Ian Richardson Email [email protected] Annabel Large Annabel in the lab. I. Richardson

222 Microbiology Today Nov 2012 Microbiology Today Nov 2012 223 Journal publishing – what happens between submission and publication?

similar work. Don’t suggest inappropriate Some large publishers operate is actually the best place for your paper; You’ve written your first paper, you’ve selected a journal to submit it to (using the reviewers – Dr Jo Blogs who works in ‘cascade journals’. Your rejection letter could it be improved and submitted advice offered in the August 2012 issue of Microbiology Today) and now you’re the lab next door may have a very good may suggest submission to an alternative elsewhere? ready to send it through the peer-review process. If you haven’t done this before it opinion of your work but would not be journal within the same publishing a suitable reviewer. In general, reviewers group. The second-tier journal will have What happens after the paper is can be daunting and there are mistakes that can be made that can either slow should not work at your institution. a lower impact factor but may still be Qaccepted? down the process or, worse still, result in the receipt of a rejection letter. Karen a suitable home for your paper. If you Receiving an acceptance letter is How should the author respond decide to pass the submission to the by no means the end of the Rowlett, Managing Editor of the International Journal of Systematic and Evolutionary A Qto reviewers’ comments? next journal in the ‘cascade’, you won’t process. In the acceptance letter, the Microbiology, gives Karen McGregor some insight into what you should expect Make sure that you prepare a need to reformat your paper and the Editor may suggest some further minor during the process from submission to publication. Aresponse to all of the reviewers’ reviewers’ comments may go with it changes; if so, make sure that you do comments. If you do not agree with a to the next Editor. This could lead to these quickly. What is your number one the journal Editor. Remember, Editors and potential reviewers for your paper. comment, give a clear reason why you a quicker decision than starting the After acceptance, your paper will be Qtip for authors? may handle hundreds of papers a year The journal website will list the names think that the change is not necessary, submission process again with a new prepared for publication by the journal’s Read and stick to the instructions and may not be fully up to date in every of the Editorial Board for the journal and don’t just ignore it. When you upload journal. However, you should think editorial team. Depending on the type Afor authors of the journal you are area – this is why they rely on specialist may give some guidance on the types of your point-by-point response to reviewers about whether the second-tier journal of journal, this may involve some copy- submitting your paper to – it seems reviewers. If you explain the relevance paper that each Editor handles. You may with your revised manuscript, it can help obvious, but it is not always done. If of your research (and possibly include also have the option to exclude individual the Editor if you create a separate version you submit a manuscript in a format references to other recently published Editors from handling your paper; think of your manuscript with the main changes that doesn’t strictly conform to the papers or papers in press), you will carefully about this and only exclude highlighted or in a different coloured font; AUTHOR instructions laid down by the journal it give the Editor a better idea of the Editors if there is a very good reason this makes it easy for them to check that is likely that your paper will be returned significance of your findings. for doing so, e.g. they are in direct all the required changes have been made. to you, delaying the whole process. If there is a good reason why you competition with your laboratory. Keep a note of the revision deadlines Submit Return Equally important is to make sure that would like a quick decision on your paper, Reviewers should have an imposed by the journal Editor. If you EDITORIAL OFFICE Decision: the contact details for the corresponding for example, to fulfil the requirements understanding of the scientific concepts know that conducting extra experiments Quick Checks manuscript is complete Reject author are correct – particularly the email for a PhD defence, let the Editor know in in your paper. If you have completed a within this time frame will be difficult, let reject and in correct format Revise address. There are a number of steps your covering letter. They may not be able literature review or attended relevant the Editor know well in advance and they Assigns an Editor Accept during the process where you will need to expedite review, but if they are aware conferences, you may be able to identify may extend the deadline for revision. to be contacted so make sure you use of the deadline they may be able to help. appropriate reviewers easily. Talk to Assign an email address that will be monitored your supervisor or other members of If the paper is rejected what are the EDITOR regularly and will be active throughout How can the author identify your department if you need additional Qauthor’s options? Reviews manuscript for appropriateness for journal the process (if you are coming to the end Qappropriate editors/reviewers suggestions. ‘Jane’ (Journal/Author Name Rejection is a reality of the process Solicits expert scientists to review of your PhD don’t use your university to suggest? Estimator, www.biosemantics.org/jane/) and some journals, particularly high- Makes final decision considering reviewers’ A recommendations email address if there is a chance that Most journal submission systems allows you to input the abstract or title of impact ones, have very high rejection that account will be closed in a few Awill ask you to suggest an Editor your paper to identify authors that publish rates. Rejection may not necessarily Request Report months’ time). mean that your paper is not of good If your paper has already been rejected by one journal, make sure that you reformat quality, it may just mean that it is not REVIEWERS What should go in the covering the manuscript according to the style of the next journal. If you don’t do this, the appropriate for that journal. Sometimes Make recommendation to the Editor Qletter? paper will be returned to you and it may also be obvious to the Editors that the paper Editors will reject a paper but encourage A covering letter is a useful way has been submitted elsewhere first (particularly if you forget to change your covering resubmission once particular problems Aof introducing your research to letter!). Editors don’t like to think that their journal might be a second choice. have been addressed. Flowchart illustrating the journal review process.

224 Microbiology Today Nov 2012 Microbiology Today Nov 2012 225 Opportunities for UG students

editing and reformatting of your manuscript. The SGM supports undergraduate (UG) students who editorial team may need to contact you at this stage if would like to experience a scientific conference. UG Grants – make they have any queries relating to your manuscript such student members who register for the SGM Spring 2013 as missing references, and inconsistencies between Conference in Manchester before the earlybird deadline the most of your results in the text and tables or figures. You may also be on Friday 22 February will not pay a registration fee membership asked to submit the source files for any images if the to attend the conference. Those who have results to versions that were submitted for review are not suitable present can apply for a UG Student Conference Grant Information on all SGM grant schemes available in for final print or online publication. to contribute towards their travel and accommodation 2013, together with application forms can be found Once your paper has been converted to journal costs. Students need not be the first author, but should at www.sgm.ac.uk/grants format, you will be sent a proof of the typeset paper. be present at the poster session to talk about their Check the deadline for returning the proof – it could work. The research being presented may have been Harry Smith Vacation Studentships be only a few days as journals often have very rigid done at any point during their UG studies, including a These studentships enable UG students to work on production schedules. Look at the proof very carefully placement year, final-year honours project or vacation microbiology research projects during the summer – this will be your last chance to check that the text is project. vacation before their final year of study. They provide correct and to put right any minor mistakes (but it is Three UG student members – Helina Marshall, support to the student at a rate of £185 per week for not the time to make extensive changes!). As you will Kathryn Turnbull & Lisa Buddrus – received funding out to be novel and not wholly what we expected, we a period of up to 8 weeks plus up to £400 for be very familiar with your paper by now it can be very from SGM to present work at the SGM Autumn 2012 thought it was worth talking about. laboratory consumables. easy to overlook mistakes, so why not get a colleague Conference in Warwick (3–5 September). Helina Attending the conference was better than I could Applications should be made by SGM members to check it too? Mark the proof up very clearly (there who had just completed a BSc (Hons) in Biological have expected – I met some really great people and who will act as the project supervisor on behalf of a is no need to use ‘proper’ proof correction symbols Sciences at Edinburgh Napier University talked to Karen attended talks about the exciting new work going on in named UG student. as long as your instructions are clear). If you need to McGregor about her experiences. different fields of microbiology (and, having just finished Closing date for applications is 15 February insert several lines of text or a reference, type this out ‘I’ve been a UG member of SGM throughout my my degree, was pleasantly surprised at how much I 2013. in an email so that there is no possibility of misread degree and I always wanted to attend a conference. understood – I was a bit worried before the conference handwriting. For part of my final year honours project I carried out that I might end up feeling a bit stupid). Presenting the Careers Conference Grants You, and your fellow authors, are likely to a 3-month full-time research project at the Moredun poster was a little daunting at first, but it was a really These grants offer UG Student Members a be asked to sign a copyright form or a license to Research Institute. When the results of the project turned great experience. Discussing my work with other people, contribution towards registration fees and cost of publish. Read any copyright agreements carefully seeing people interested in my results and getting Helina Marshall (left) travel to a Life Sciences Careers Conference. Aimed and make sure that they do not conflict with the their suggestions of what could be done next with my and Kathryn Turnbull at UGs and recent graduates, the conferences include policies of your institution or funder. If your funder or research was really inspiring. I just generally enjoyed the (above right) presenting presentations covering a wide range of science-related institution has a policy that published research should their posters at the SGM whole conference experience! It has definitely made me subjects, a CV workshop providing tips on how to be open access, you may have to arrange Autumn 2012 Conference at more certain about continuing into a career in research secure an interview for your perfect job, and a to make a payment to the publisher at this stage. the University of Warwick. and I have just started on a BBSRC interdisciplinary I. Atherton chance to mingle with the experts exhibiting at the Once that is done, you can sit back and look doctoral training programme based at University College conference and ask informal questions over lunch forward to seeing your name in print – or get started London.’ and afternoon refreshments. on your next paper and go through the publication The 2012 conferences are taking place at process all over again! Lisa Budruss gave an oral presentation entitled Electricity generation in MFCs using distillers’ dried University of Birmingham on Wednesday 14 grains with solubles and recorded a podcast with the November 2012, Queen’s University Belfast on SGM Press Officer about her work. Listen at Wednesday 28 November 2012 and University of http://bit.ly/RWGvCO Leeds on Wednesday 5 December 2012.

226 Microbiology Today Nov 2012 Microbiology Today Nov 2012 227 interview

Ian Boyd Defra Chief Scientific Adviser

SGM would like to congratulate but the changes in the structure of as partly being there to explain the this isn’t a case of one type of research The marine environment and What are your aspirations for the Research Excellence Framework delivery mechanism being better than microbiology you on your new appointment rationale, based upon the evidence, for Q Defra’s research on infectious towards recognition of impact have why Defra needs to take certain views another. The real question concerns how, You have had a distinguished diseases of crops and livestock? as Chief ScientificA dviser to changed this. I was very fortunate to and build policies that sometimes might in functional terms, each one delivers Q career in marine biology, and The UK agricultural system, Defra, and wish you well in the have understanding management at appear counter-intuitive. This is not just high-quality science to support societal microbiologists have a particular interest A including forestry, is probably role. We appreciate that you’ve St Andrews. The main message is that about ensuring that policies are firmly objectives and on what time scales. in disease in aquaculture, natural under greater stress from new infectious intellectually agile individuals, wherever grounded in core science, but it is also Each institution presents a different products from marine micro-organisms diseases now than at any time in history. not had much time to get to they are and whatever they are studying, about integrating this with social and profile in that respect and consequently and microbial pollution (algae and This presents a critical national challenge grips with the full gamut of should have the capacity to connect economic evidence and being able is optimised differently. I can fit into this bacteria). Does Defra have any particular and it is not just Defra that has to responsibilities you will have from their research with societal benefits and to take a long-term view. It is hard to by helping Defra to exploit this diversity plans in these areas you can tell us step up to meet this but the research should be continually exploring and persuade people of the benefits of a by drawing down the best quality September, but nevertheless we about? community as a whole. However, it is probing how best to achieve this. If I policy that is designed to smooth our of evidence from across the whole I have spent my career studying Defra’s job to take a lead in tackling have a few questions on your can help to significantly raise the game path over decadal time scales when it spectrum of providers and also to provide ‘big things’, basically from very non-indigenous crop diseases both in of the science research community with is not seen to have tangible benefits constructive feedback about how the A work as it relates to the interests large multicellular organisms up to terms of providing targeted resources respect to how they work within policy here and now. Communicating these flow of evidence could be improved. of our members. large-scale ecosystems. However, one and developing strategies that others and with industry then I will have made concepts is extraordinarily difficult and of my interests is in scale-free processes can align with. This needs to include the a difference. We are faced with some a priority for me is to both listen to Your aspirations as Chief so the size of ‘things’ becomes less whole spectrum of control measures massive challenges over the coming people’s concerns and to explain the Scientific Advisor relevant. As I said in a recent perspectives from protection and mitigation through decades and I want the best and most evidence upon which policies are based. to adaptation, when we are aware that How do you think your career so piece in Science, the dynamics of yeast imaginative minds to be brought to bear Defra already draws on a wide protection and mitigation are unlikely far has helped prepare you for the cultures can help to explain the dynamics Q on coming up with solutions. portfolio of scientific expertise to work. But, at the centre of this will role of Defra Chief Scientific Adviser? Q of much larger-scale systems. I find The government has emphasised – in its own research establishments, also be communication both within the Are there lessons for our members the whole idea that the same basic agriculture as a route to ‘export- in agriculture and industry, in research community to help align the who wish to take a role in setting and Q mechanisms govern dynamic systems led growth’. From some angles, Defra institutes funded by the Research best minds to tackle the most pressing implementing policy at a senior level? from the very small to the very large can sound like the old Ministry of Councils, in learned societies, and problems in a way that will likely make What are your ambitions in the role? utterly gripping; if we can find the Agriculture! But the department now in universities. How will your role fit fundamental key to understanding these a difference, and with the public whose My career has seen me spend has many additional responsibilities. How into this network? common processes then we will have lives, livelihoods and environment might considerable time in both research A do you see the relative emphases in your The UK has a rich and diverse made a major intellectual leap forward. be seriously altered as a result. institutions and universities so I am new role – and where do your priorities mixture of mechanisms for Bringing this back to the very real What balance between endemic aware of the structural, cultural and A lie? undertaking scientific research. I problems of biosecurity, the exploitation and (potential) ‘exotic’ disease functional differences among these Q Some of the old images of ‘The think this is one reason why the UK, of microbial processes and managing threats do you think works best in the research delivery bodies. Added to this, Ministry’ are certainly hard to shake considering its size, has been and microbial ecology is a very important research and surveillance portfolio? as an academic researcher I made a A off. This is partly because Defra retains remains a leading global economic challenge. specific point of spending time working Livestock diseases can have the old role of regulator in agriculture power. I sometimes get frustrated by on policy-related issues. I made an A significant economic, social and and fisheries, and this is now extending narrowly focussed metrics produced Crop and livestock diseases intentional choice to sacrifice time that environmental costs in addition to to other uses of the environment. There by individual institutions to make them I could have spent following my own Crop and livestock diseases – a big compromising the welfare of affected is a very real image problem associated look better than others. We all know research interests in order to oil the issue, and a complex one, but also animals. Also, an outbreak of an exotic with this because it is all too easy for that different institutions play different wheels at the science–policy interface. one very dear to the professional lives notifiable disease can have severe Defra to be seen as a bureaucracy that roles in the mixture. While there are This was deeply unfashionable within of many of our members. Three trade implications for the UK economy. interferes in people’s lives. I see my role weaknesses which need to be addressed, universities even just a few years ago questions: Defra’s current research and surveillance Ian Boyd. Defra

228 Microbiology Today Nov 2012 Microbiology Today Nov 2012 229 Marjory Stephenson and me

Hilary Lappin-Scott portfolio funds work on a number of of the occurrence of problems with How can scientists avoid getting There is a need for greater diversity in our different diseases, both endemic and microbial food safety. The major problem eaten alive – or do scientists have exotic, and it is important to remember is assessing the extent to which these nothing to fear from these ‘majestic scientific ‘mixed community’ to strengthen that they are not mutually exclusive. For predictions might be challenged by the predators’? microbial sciences and the SGM. example, adherence to strong biosecurity effects of climate change or changing My experience of working with principles for endemic diseases may human behaviour. The early detection of A politicians and policy people is At first glance Marjory Stephenson and I do of my usual activities and increases my reduce the potential impact of an exotic trends is essential and, like any infectious that they are really not very different not have much in common. She went directly into awareness to the real concerns of early- disease. Defra’s surveillance programme disease that affects people, there needs from scientists. The competitive nature academia from school, was one of the first two females career microbiologists (males and females) Marjory Stephenson. SGM is targeted towards the detection of to be a strong link between health of scientific research certainly doesn’t (with Kathleen Lonsdale) to be elected to the Royal who are considering their future and how new and re-emerging threats, aligned screening through the NHS and the leave much room for the faint-hearted Society and served as President of the SGM immediately to balance careers with family life. The with a reactive research programme response to an outbreak. or thin-skinned these days. In general, after Alexander Fleming in 1947–1949. As the years EU podcast has already been covered by enabling us to respond effectively. On What position do you take on the we are all rational people who make rolled by, the SGM rose in eminence, successive others, I consider that it captures much of the question of whether we always have Q use of antibiotics in agriculture? decisions based upon a combination of Presidents were appointed, but we had to wait until the complexity of how to attract all sections the balance that works best – that is a 2009 before a second female held this office (me), a of society into science. Antibiotic resistance is a major the evidence available and prejudice or question that is difficult to answer, but period of some 60 years after it was held by Marjory The presence of more males in senior problem and we need to properly belief. What distinguishes scientists from I recognise that it is vital to constantly A Stephenson. I worked for several years before going to roles is often attributed to committees assess the costs and benefits of antibiotic the others is that they perhaps lean more monitor and evaluate our research and University, I am the first scientist/academic in my family considering only those ‘in our own images’ use. It would be easy to just say we towards decision-making based upon surveillance programme to ensure that it and briefly held the SGM Presidency concurrently with when choosing who to invite to give talks, should stop all antibiotic use, but there evidence, at least professionally. Scientists continues to address the threat. What is that of the International Society of Microbial Ecology. to be awarded scientific distinctions, to sit are likely to be key types of uses that have a very important general mentoring important is that we maintain the UK’s Thankfully, there are now more women in the on prestigious committees, and who to present greater problems than others. role in trying to make others think expertise and capability to act quickly workforce than in Marjory Stephenson’s time, but encourage to apply for top jobs, etc. Suffice I also have to point to innovation as a outside their box, often by presenting no matter whether that threat is from generally they occupy the lower levels, with few to state that this draws on a limited section route through this problem. Not only evidence in ways that cause others to Hilary Lappin-Scott. I. Atherton, SGM an exotic, endemic or indeed a new and reaching the top jobs in industry, government or of the talent pool, to the detriment of our do we need a continuous stream of question their prejudices or beliefs. I re-emerging disease. academia. Microbiology attracts many females at discipline, and is a cause of growing concern within SGM. new antibiotics, perhaps even more may be proved wrong, but I think the undergraduate and postgraduate levels, but the When I completed my 3-year term of office as The issue of microbial food safety importantly, we need to adapt our metaphor of the killer whales prowling numbers then dwindle with every successive step up the President in September, Council asked me to establish Q is always with us and occasionally systems of agriculture to be much more Whitehall is not really accurate. Certainly, academic ladder, often referred to as the ‘leaky pipeline a new initiative as SGM Diversity Champion, to work erupts as a crisis. How will you scan for aware of biosecurity. I suspect there is there are some difficult trade-offs to be of talent’ (www.royalsoced.org.uk/cms/files/advice- to promote greater gender and ethnicity diversity by impending crises, gauge their scale, and a lot that can be done to achieve this, made at the top level of government papers/inquiry/women_in_stem/tapping_talents.pdf). tapping more widely into our talent pool. A Working communicate the risk to ministers? How mainly representing relatively simple and one can find oneself on the losing Throughout my career I have of course been aware Group will shortly be set up to support this; however, can professional microbiologists and control measures, but the challenge is end of an argument, but we live in such that at each career stage there have been fewer and I am keen to hear all ideas from the membership, to learned societies like SGM assist you in in communicating this and incentivising an imperfect world that one cannot fewer females around the table with me. I have always aid our success. Similarly, the Working Group will seek horizon-scanning? individual practitioners to implement afford to take the rough time personally. considered that the best way to address this was to lead to learn from and work with other learned societies to The issue of food safety sits with these measures. I would encourage more scientists to by example, by striving to be a strong role model in all address issues of equality and diversity. the Food Standards Agency, but get involved and not to be afraid to do A my activities and to mentor female and male early- and After all, we understand all too well that monocultures it is right that Defra should take an And finally… so. Even if you do feel you have been mid-career scientists. I enjoy these roles and consider do not reflect nature and that diverse communities give active interest in the issue, especially ‘eaten alive’ in the process, it can be very Your website refers to that they are part of the job. the greatest stability. We are determined not to wait where environmental factors are a rewarding to see your ideas taken up Q your scientific interest in the This changed when I became more involved in another 60 years before there is another female President. major cause. Defra invests heavily in the by the government machine and used, ‘Behavioural dynamics of marine social media and, significantly, because of the recent EU assessment of risk and it is possible to hopefully, towards a positive outcome predators’. There are almost certainly campaign Science: It’s a girl thing. Social media gives Hilary Lappin-Scott develop reasonably accurate predictions for society. a few killer whales lurking in Whitehall. me daily access to a wide range of opinions outside Email [email protected]

230 Microbiology Today Nov 2012 Microbiology Today Nov 2012 231 sGM journals

All SGM journals …Fair! …Free! …Fast! …Far-reaching! are not-for-Profit Specialised and expert No submission or page Accepted manuscript online All papers open access after 12 months (2 years for IJSEM) and… international editorial boards charges within 7 days Long cited half-lives and indexing in Medline ensure a global ensure high-quality peer review readership

mic.sgmjournals.org Microbiology, published ijs.sgmjournals.org IJSEM is the official monthly, combines journal of record for editorial expertise from novel prokaryotic names around the world with of the International exceptional breadth of Committee on Systematics coverage and high-quality of Prokaryotes (ICSP) of Current production standards, and the International Union of impact provides access to topical, Current Microbiological Societies factor high-quality research and impact (IUMS). The journal is 3.061 up-to-date reviews in a factor the cornerstone of the single accessible source. 2.268 dynamic field of microbial systematics.

Editor-in-Chief Agnès Fouet (France) Reviews Editor Editor Stephen Spiro (USA) Aharon Oren (Israel) jmm.sgmjournals.org JMM, published vir.sgmjournals.org JGV is a dynamic journal monthly, is one of the at the forefront of virology leading peer-reviewed today. Established for 45 journals in the field, years, JGV publishes high- Current Current publishing high-calibre quality virological research impact impact research papers, reviews, from around the world on factor factor editorials, case reports and a monthly basis. 2.502 3.363 correspondence articles on medical, dental and veterinary microbiology and infectious diseases from around the world.

Editor-in-Chief Editor-in-Chief S. Peter Borriello (UK) Richard Elliott (UK) Reviews Editor Reviews Editor Kim Hardie (UK) Tony Minson (UK)

232 Microbiology Today Nov 2012 Microbiology Today Nov 2012 233 Designer microbes make an appearance at SGM

Rocky Cranenburgh

bioethics considerations will influence Synthetic biology is a rapidly growing area of applied the development of synthetic biology, biotechnology that represents the fusion of genetic engineering and Joyce Tait (Edinburgh) discussed with an increased understanding of the complex workings of cells the way that social scientists view that has come from genomics, transcriptomics, metabolomics and technological advances, focussing on systems modelling. To highlight the latest developments in synthetic approaches to achieve smarter and more biology, there will be a special themed issue of SGM’s journal flexible regulation. Synthetic biology is not restricted Microbiology in July 2013 and papers are invited for submission to industrial applications, and biomedical from now to mid-January 2013. applications are still of the greatest There is no universally accepted necessitate a detailed understanding of commercial importance. Michael definition of synthetic biology, but while biochemical pathways to identify the best Bromley (Manchester) described the it certainly encompasses applications of bacterial candidates as ‘exoelectrogens’, use of synthetic biology approaches in genetic engineering and biotechnology, and the development of engineering a screen to identify novel antifungal it is fundamentally about the design and solutions to maximise their potential. drugs. Our work at Prokarium (presented the introduction of new components Biofuel production is an area where at the SGM Spring 2012 conference or biosynthetic pathways into cells, or microbes could have an important role. in Dublin) utilises live Salmonella that the adaptation of existing pathways to David Leak (Bath) described his work on contain modified genetic circuitry to produce novel compounds or features. ethanol production using thermophiles, achieve selectable marker-free plasmid While traditional genetic engineering Thomas Howard (Exeter) focussed on maintenance and targeted antigen gene often involves mutating a chromosomal transport fuel production in Escherichia expression for oral vaccine delivery. gene or inserting a new gene, synthetic coli and Aindrila Mukhopadhyay The presentations at the Designer biology describes the manipulation of (Berkeley) described the use of microbial microbes symposium gave an overview biological systems, enabling cells to be efflux pumps for biofuel tolerance and of the applications of synthetic biology, designed that are capable of carrying production. indicating some of the areas that we are out novel functions and/or producing Micro-algae are being developed to interested in for the Microbiology special new compounds. Recent developments produce biofuels and other products, issue, but we welcome articles on a wide in the enabling technologies, such and Saul Purton (UCL) described the use range of synthetic biology topics and as DNA sequencing and synthesis, of DNA components called ‘Phycobricks’ look forward to an interesting issue have revolutionised what is potentially in synthetic biology applications of that will help to define this new and achievable by synthetic biology. Chlamydomonas reinhardtii. Cellulosic exciting field. At the SGM Autumn 2012 biomass is an abundant and under- Papers for the special issue must conference in Warwick, I co-chaired utilised resource, and Chris French’s be submitted by mid-January 2013. a symposium on Designer microbes, group (Edinburgh) engineer cellulose- Full details about the scope and how which featured innovative advances in degrading E. coli and Citrobacter freundii to submit are available at http://bit.ly/ synthetic biology. Justin Buck (Cambrian using enzymes identified from a range PCbKVh Innovation Inc.) and Lisa Buddrus (Surrey) of other bacteria. Genetic engineering described the use of bacteria to generate tools are critical to synthetic biology and Rocky Cranenburgh electricity in microbial fuel cells. Although Nigel Minton (Nottingham) described Chief Scientific Officer, Prokarium Ltd; these approaches do not necessarily his ClosTron system for modification of Email [email protected] involve genetic modification, they do Clostridium spp. Public perception and

234 Microbiology Today Nov 2012 Microbiology Today Nov 2012 235 Reviews SB’s new HE teaching website promotes Open Education Resources

Eva Sharpe

This summer, the Society of Executive Committee to ensure the don’ts’ for creating your own resources. project meets the needs of those The uncertainty over whether Influenza Virus: Methods and Protocols Microbes and Evolution: The Biology (SB) received funding working in HE, we have focused on institutions allow and encourage their Edited by Y. Kawaoka & G. Neumann World That Darwin Never Saw from the Higher Education resources that support practical biology staff to create and release OER is Academy and JISC through Published by Springer-Verlag GmbH & Co. KG (2012) Edited by R. Kolter & S. Maloy and research-led teaching in HE. something we all need to address as a their Open Education Resources £85.50 pp. 234 ISBN 978-1-61779-620-3 Published by American Society for Over the summer we surveyed the community. Institutional policy needs Microbiology (2012) (OER) Programme. We were to biosciences community to find out what to be disseminated and embedded at This book really does do ‘what it says on the tin’. One of the US$14.95 pp. 299 ISBN 978-1-55581-540-0 work with our Special Interest they would find most useful from the a departmental level and departments Methods in Molecular Biology series, it covers much more than Group, the Heads of University website. We asked about current use need to make it clear what staff just molecular biology. Chapters cover a comprehensive list Initially stimulated by the bicentenary of Darwin’s Biosciences (HUBS), to identify, and barriers to using OER and comments training is available to support this. of topics, such as virus isolation, characterisation of the virus, birth, this collection of essays discusses how collect and promote UK OER on our plans for our website. In our work with departmental serological methods, diagnosis of influenza, laboratory assays, microbes fit evolution as Darwin would have animal models, surveillance, molecular virology techniques, genetic to the bioscience community. In response to our suggestion that heads through HUBS, and teaching understood it. There are good examples of classical analysis and genetic engineering of the virus. The chapters are all Through this project, we have we focus on practical biology resources, practitioners in our membership Darwinian evolution and cases where we have to extremely informative both for a new researcher in the field or for bend our ideas somewhat. recently launched a new respondents felt that lab and fieldwork and beyond, we will be promoting the more seasoned flu researcher, and I think this book would be a Higher Education (HE) teaching protocols, data handling exercises, institutional change to support the use Metaphor is a powerful tool for conveying concepts valuable addition to the laboratory bookshelf. Influenza virus videos of techniques and multimedia of OER and championing reward and to a lay audience. Unfortunately, it ends up being website at http://heteaching. will continue to challenge and no doubt surprise us. This really is alternatives to wet lab work would be recognition for those involved. confusing when the metaphor shifts every few societyofbiology.org a multi-disciplinary book, which I personally think is very beneficial, the most useful resources to feature. Setting up this new website to pages. This is not, then, a book to be read from as influenza researchers need to be able to approach research OER are learning, teaching and Feedback from those already using promote the use of OER has been the cover to cover, at least not in one sitting. It is from all angles to try to stay one step ahead of an ever evolving research resources freely available for OER highlighted that although there start of this project for us, and we look also unclear at whom this book is aimed. Many virus. the teaching community to use and was a number of very good resources forward to working with you all on this chapters would be clear to any intelligent reader, adapt that have been released under available, there was a huge variety in in the future. We will be adding new Ruth Harvey, National Institute for Biological Standards & but others seem to be written for an audience of specific intellectual property rules. There the quality, and a great deal of searching resources as they are released to keep Control microbiologists or molecular biologists. That said, are many excellent teaching resources and sorting was needed to find high- the website up to date and useful. there are some excellent essays in this collection and publicly available across various websites, quality resources. To address this we have If you are creating new resources, or Systems Microbiology: I shall use ideas from it when teaching the concept publications and discussion forums. included an element of peer review in know of a great resource that we have Current Topics and Applications of microbiology to general biologists. Although some of these resources are the project, recruiting a team of experts missed, then please let us know via the David Roberts, The Natural History Museum featured in specific sites, such as the in the bioscience teaching community to ‘Submit resources’ section of the site! Edited by B.D. Robertson & B.W. Wren UK’s national repository for OER, Jorum, review all of the resources we find. For more information on the Published by Caister Academic Press (2012) many are hosted directly on institutions’ When asked about the main barriers project please see http:/heteaching. £159.00 pp. 170 ISBN 978-1-90823-002-7 own websites and may require extensive to creating OER, the overwhelming societyofbiology.org This compact volume contains contributions from many well-known names in the field of systems microbiology. searching to find them. response was, unsurprisingly, that of Dr Eva Sharpe The book opens with an overview of modelling approaches which, as an experimental microbiologist, I found The project allowed us to identify time, but many responded that they did HE Policy Officer at the Society particularly interesting and valuable. This is followed by chapters on microbial phenomena, such as chemotaxis resources for bioscience HE, and signpost not know how to go about releasing of Biology; Email evasharpe@ and phagocytosis, and on the metabolic pathways of single species of bacteria and archaea. The theoretical them to the teaching community via their teaching materials as OER, or societyofbiology.org and modelling approaches presented within these case studies are clearly explained and, similarly, the biological a new website, reducing the time even whether their institutions would information is written in such as way as to make it accessible to non-specialists. Each chapter contains spent by individuals searching the allow this. Resources such as the JISC useful websites numerous references for those interested in investigating a particular topic in more detail. The wide range of web, ensuring better access to quality OER infokit and STEM OER Guidance www.heacademy.ac.uk biological and modelling topics covered would make this a beneficial purchase for any institution or systems teaching resources, and introducing and wiki provide information on using and www.jisc.ac.uk biology consortium. Overall, this is a valuable resource that will appeal to experimentalists and modellers alike. encouraging those who are new to OER. creating OER, covering copyright and www.societyofbiology.org/hubs Alison Graham, Newcastle University Working closely with the HUBS intellectual property issues, and ‘dos and www.jorum.ac.uk

236 Microbiology Today Nov 2012 Microbiology Today Nov 2012 237 Comment

Tracey Guise & Laura J.V. Piddock

written in newspapers and magazines Genome Plasticity and Troyte Griffith, Malvern Architect and broadcast on radio and television. Infectious Diseases and Elgar’s Friend Antibiotic Action gained a respectable following on Twitter, an Early Day Edited by J. Hacker, U. Dobrindt & R. Kurth By Jeremy Hardie Motion was presented to the House of Published by American Society for Published by Aspect Design (2012) Commons and thousands of individuals Microbiology (2012) signed the online petition. It was an £12.50 pp. 164 ISBN 978-1-90883-210-8 US$159.95 pp. 416 ISBN 978-1-55581-708-4 explosive start to an initiative that began Having reached the dizzy heights of Professor in Microbiology, by examining why, after over a decade Variety is, supposedly, ‘the spice of life’. In the retirement looms. But what happens of esteemed publications, committees, case of infectious agents, however, it is a matter of then? Is there anything from all those reports and professional concern, survival. Genomic plasticity in infectious agents is years of knowledge acquisition and they had failed to generate sufficient alteration of the sequence of genes so that different experience that can be combined interest to prevent the rapid decline in sequences are expressed or the original sequences with the gardening and holidays? Do antibacterial drug discovery research and are expressed at different levels. This phenomenon all those hard-earned skills have to development. allows those infectious agents to adapt and survive be lost the day one walks out of the So almost 12 months on, what has changes in their environmental conditions. In the department? A recent publication Antibiotic Action achieved? Highlights context of infectious disease, the environment exemplifies how well the training in include: includes the host, so genomic plasticity in the host research investigation, writing and ‘If health fails, She had just spoken of the need to – Collaborations with international organism also has to be considered. This book presentation can be reborn in a very tackle the major health and social issues groups, including ReACT, the describes examples of genomic changes occurring satisfying way. all else fails’ required to meet the WHO Millennium Infectious Diseases Society of in medically important bacteria, viruses, fungi and Development Goals leading to improved Deep in Elgar’s homelands amongst America, Alliance for the Prudent protozoa, as well as examples of genomic plasticity said Margaret health for all by 2015. High on the list of the beautiful Malvern Hills, curiosity drove Emeritus Professor of Use of Antibiotics and L’Alliance that occur in man that affect susceptibility to these stated priorities was the need to tackle Oral Microbiology (St Barts and the London School of Medicine Chan, Director (representing 27 EU nations). agents. Changes can occur by rearrangement within the continued rise in antibiotic-resistant and Dentistry, University of London), Jeremy Hardie, to find out – Meeting the Health Minister Simon an organism’s own genome or by the addition or bacteria and the lack of development of more about the history behind the house he bought to enjoy his General of the Burns and civil servants in the exchange of genetic material from outside, and any new antibiotics. retirement in with his wife Margaret. Why did the architect who Department of Health. We now genomic change that enables an infectious agent to World Health Her words resonate loudly with designed the house become immortalised by Elgar because one provide briefing documents. survive, flourish and, in some cases, cause disease, Antibiotic Action, the UK-led global of his Enigma variations bore his name? Unlike most of the other Organization – Meeting the Shadow Health Minister in an environment made evermore hostile by the initiative that exists to inform and subjects of Elgar’s portrait gallery, Troyte Griffith was not a gifted Jamie Reed, and provision of presence of antimicrobial drugs or host immune educate all about the need for musician. (WHO), in her questions for the Prime Minister to responses, will be to the agent’s advantage. discovery, research and development answer in the House of Commons. The book brings together the architectural impact that Troyte The book would benefit from the inclusion an 62nd address of new antibacterial drugs. Launched – Provision of administrative Griffith had and delves into his relationship with the famous introductory chapter describing the basis of genomic at the Houses of Parliament in support to establish the All Party composer in a readily readable way with lots of interesting to the Regional change and its relevance to infectious disease, and November 2011, the initiative received Parliamentary Group on Antibiotic illustrations. also by having abstracts in each chapter. The book Committee unprecedented interest and support. Discovery and Development. will be of interest to anyone studying infectious With acclaim in the local press (Malvern Gazette and Birmingham Organisations across the globe sought – Providing the momentum to diseases but its price will certainly limit purchase to Post), the book is available at several bookshops and libraries for Europe in to partner and support Antibiotic stimulate revision of the regulatory institutions. specialising in local history, architecture or music-related material. Action, manuscripts were accepted and processes for licensing new September published by esteemed international Christopher Ring, Middlesex University Kim Hardie, The University of Nottingham antibiotics. 2012. peer-reviewed journals, stories were – Discussions with the WHO to

238 Microbiology Today Nov 2012 Microbiology Today Nov 2012 239 Microbiologysociety for general

Spring Conference 25–28 March 2013 Manchester

help them deliver their action plan on antibiotic It has been proposed by many that it is financial resistance – particularly in the area of public incentives that will tempt industry to re-enter/continue engagement. to discover, research and develop new antibacterials – Facilitating public awareness and engagement as drugs for patients, and the recent GAIN Act in the by establishing an international network of USA and the EU Innovative Medicines Initiative seek to Antibiotic Action Champions – some of whom do this. It has been suggested by some that neither of have already successfully ‘flown the Antibiotic these will have much impact; however, it is impossible Action flag’ at student festivals and international to determine what the outcome will be and it is almost conferences. certain that it will take many different strategies and – Discussions with major funding bodies, such as funding streams to resolve the situation. In particular, the BBSRC, MRC and Wellcome Trust, on what as microbiologists we must fight for our discipline to Submit your abstract and Register now to can be learnt from industry to understand why be heard equally with others that have high profiles. To some drug discovery programmes have not do this we must make sure that the fantastic advances be part of the SGM Spring network at Europe’s yielded new drugs. being made in academia are publicised and that there The need for new antibiotics and the devastation are mechanisms to facilitate development into new Conference 2013 at Manchester largest annual gathering the absence of antibiotics will wreak is undeniable. drugs. Links between academia, SMEs and Pharma However, it will take time to alter perceptions about require strengthening and new funding routes. In this Central Convention Complex, of microbiologists. the urgent need to develop new antibiotics – that or way we can ensure that we retain the existing expertise a cataclysmic event to grow public understanding – and attract the brightest young minds to our fields of featuring Nobel Prize Winner just think of the furore if Prince Philip’s recent bladder research, to discover and develop antibacterial drugs of infection had been caused by an antibiotic-resistant the future. Antibiotic Action will continue to stimulate Harald zur Hausen. bacterium which proved untreatable. We need to activities across disciplines to ensure new effective change the perception that antibiotics have failed – treatments are available. After all, without antibiotics they have not – they are one of the miracles of modern the health of nations will fail – a fitting adjunct to the medicine and the reason why many of us have reached quote by Margaret Chan. www.sgmmanchester2013.org.uk adulthood today and will reach the extremes of age. As TRACEY GUISE, CEO British Society for Antimicrobial there is no collective memory of the pre-antibiotic era, Chemotherapy (BSAC) & LAURA J.V. PIDDOCK, Professor the public voice is small, unlike that for other diseases of Microbiology, University of Birmingham, BSAC Chair in such as cancer that many people are afraid they will Public Engagement and Director of Antibiotic Action (Email Conference highlights die from. Antibiotic Action seeks to raise the voice [email protected]) to a deafening level so that everyone is aware that We continue to seek new Antibiotic Action Champions, Viruses and human cancer Metabolic interactions antibiotics underpin much of modern medicine from the remit of whom is simple, to inform as many people as trauma to transplant surgery to joint replacements, possible of the need to discover research and develop new and that infections are commonplace in these settings; antibacterial drugs. If you wish to be a Champion please see RNA – more than just a Co-infections and Scan here governments and policy-makers must sit up, take note the website for the resources we provide http://bit.ly/SHK5TC and act. or contact Laura Piddock. genome co-colonisation for further conference Antimicrobials Bacterial–fungal interactions info. 240 Microbiology Today Nov 2012 Exploiting Streptomyces Virology workshopsMicrobiology Today Nov 2012 241

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