Microbiology Society Since 2016 and Won the 2018 Sir Howard Clarity to the Larger Picture, and Open Dalton Young Microbiologist of the Year Prize

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Microbiology Today 46:2 May 2019 Metabolism, Health and Disease and Health 2019 May Today 46:2 Metabolism, Microbiology 46:2 May 2019

Metabolism, Health and Disease

Where bacterial metabolism and virulence intersect How sialic acid impacts on metabolism, health and disease Modelling virus infections of the skin in 3D Human noroviruses and gut bacteria: friends, frenemies or both? The intestinal microbiota in health and disease health and disease are yet to be Ghannoum M, The Scientist. The investigated, and who knows what Mycobiome;2016. https://www.the-scientist. Why does microbiology matter? implications these will hold for human com/features/the-mycobiome-34129 Farhana: Microbes include a hugely health. [accessed 26 February 2019]. versatile range of organisms. They Hall RA, Noverr MC. Fungal interactions with are integral to the functioning of most Further reading the human host: exploring the spectrum of ecosystems, yet we are still in our Dhamgaye S, Qu Y, Peleg AY. Polymicrobial symbiosis. Curr Opin Microbiol 2017;40:58–64. infancy in understanding their impact. infections involving clinically relevant Gram- Quinton, J. Fungal mediated innate immune Courtney: Micro-organisms coat every negative bacteria and fungi. Cell Microbiol memory, what have we learned? Semin Cell surface around us, on us, and in 2016;18:1716–1722. Dev Biol, in press. our bodies. By understanding how microbes function and how they can Courtney Kousser impact us, we can better learn how to Institute of Microbiology and Infection, School of Biosciences, work with them or fight them. University of Birmingham, Edgbaston, Birmingham B15 2TT, UK Rebecca: Studying all aspects of e [email protected] microbiology is important to enhance @cakousser our understanding and to make new Courtney Kousser is a fourth year PhD student in Dr Rebecca discoveries. Microbiology has been A Hall’s lab. Courtney’s research focuses on the interaction at the heart of identifying the basic Courtney Kousser Courtney between the deadly fungus, Rhizopus microsporus, and the principles of life for decades. Even opportunistic bacterium Pseudomonas aeruginosa within the host. She has been small pieces of the puzzle provide a member of the Microbiology Society since 2016 and won the 2018 Sir Howard clarity to the larger picture, and open Dalton Young Microbiologist of the Year Prize. new avenues of exploration. At heart, everyone is a microbiologist, they Farhana Alam might just not know it. Institute of Microbiology and Infection, School of Biosciences, What advice would you give to University of Birmingham, Edgbaston, Birmingham B15 2TT, UK someone starting out in this field? e [email protected] Farhana: Read widely and don’t limit @_farhana_alam yourself to your specific research Farhana Alam is a second year PhD student working in area. There is much to be gained Dr Rebecca Hall’s lab. Her research, in collaboration with from inter-disciplinary learning; like Farhana Alam Farhana Dr Jessica Blair, focuses on fungal–bacterial polymicrobial any other form of life, microbiology biofilms and their effects on antimicrobial resistance. does not occur in isolation! Courtney: Attend conferences, Rebecca Hall speak to the intimidating Principal Institute of Microbiology and Infection, School of Biosciences, Investigator, and step outside of your University of Birmingham, Edgbaston, Birmingham B15 2TT, UK comfort zone. You’ll gain confidence e [email protected] and become an active, well-rounded @BECKS_182 member of the community. hall-fungal-research.co.uk Rebecca: One of the best ways to get to Rebecca Hall is a current MRC-funded Career Development know people, and the field, is to go to Rebecca Hall Rebecca Award Fellow and Lecturer in Microbial Adaptation at the a conference, to hear lots of excellent University of Birmingham. Rebecca is interested in how microbes adapt to the science, ask questions and share environment of the host and the consequences this adaptation has on disease ideas. Also, the fungal community progression. She has been a member of the Microbiology Society since 2014, and may be small, but we are mighty, is a member of the Eukaryotic Division. collaborative and enjoy a good dance!

Microbiology Today May 19 | microbiologysociety.org 97 Editorial

Welcome to the May edition of Microbiology Today, and up for investigation in this edition are microbial metabolism, health and disease. The ability of microbes to metabolise different substrates enables them to thrive in a vast diversity of niches, including various parts of the human host. The way microbes interact with metabolites influences how they affect the health of their host and can be linked to disease. This month our authors explore the fascinating range of ways in which these microbes and their metabolism can impact health. Whole Picture

o start us off on this theme, Moving from bacteria to disease. Starting with the microbiome Kim Hardie reflects on how viruses, Sally Roberts and Joanna in early life and highlighting the factors T metabolism and the ability Parish consider how the development of that impact on the health of our to utilise essential nutrients forms organotypic raft cultures has improved microbiome, they consider the impact the basis of a healthy microbial cell. our ability to study virus infection of bacterial products on host health. Revealing some of the many complex strategies. Explaining the basics of With research increasingly making interactions linking metabolism and this technology, they describe how links between dysbiosis and disease, virulence, Kim demonstrates how these rafts can be used to form fully Katherine and Simon address the these two factors are intertwined and differentiated epithelia. They explain complexities of this area of research, can influence bacterial fitness within how these organotypic rafts have been the available evidence and the a population. Kim explains how these used to gain insights into the replication therapeutic potential in this area. complex interactions can influence of herpesviruses, such as Epstein–Barr The Comment piece for this edition infection severity and concludes by virus, and how they could be used in the is written by Courtney Kousser, Farhana providing some perspectives on how future to support the testing of antivirals. Alam and Rebecca Hall, and looks at the new technology could help further Staying with viruses, Matthew importance of fungi, their interactions elucidate the intricate relationships Moore discusses the difficulties in within the human microbiome and the between metabolism and virulence. controlling norovirus, the outcome of roles they can play in health. Explaining Next, Andrew Bell, Emmanuele infection (spoiler, it’s not good) and the range of interactions fungi can have Severi, Nathalie Juge and Gavin Thomas the complexities of in vitro cultivation with other microbes, they highlight how explore the various functions of sialic of norovirus. Historically difficult to fungi can provide a route for bacterial acid. Sialic acid is a metabolite of cultivate; it was only in 2014 that dissemination, as well as impacting on significant importance in bacterial– successful cultivation and replication the virulence of polymicrobial biofilms. host interactions. Our authors outline of norovirus in human B cells was The rising antimicrobial resistance of the strategies microbes have devised achieved, using enteric bacteria as a fungal pathogens and their ability to for utilising sialic acid for different co-factor. Matthew reveals the advances modulate the host immune system purposes. They reveal the ways in which in this field since 2014 and addresses makes these microbes a fascinating both commensals and pathogens can the questions which will need to be part of the microbial world. use sialic acid, for example as food and answered to take this research forward. for camouflage. They then explain how We stay with the intestinal Rowena Jenkins sialic acid has inspired antiviral design theme as Katharine Seton and Simon Editor and could be utilised for future anti- Carding walk us through the role of [email protected] infection purposes. intestinal microbiota in health and

Microbiology Today May 19 | microbiologysociety.org 49 Contents

Microbiology TODAY Articles Where bacterial metabolism and 58 virulence intersect Kim R. Hardie Interactions between metabolism and virulence.

A special sugar: how sialic acid impacts 62 on metabolism, health and disease Andrew Bell, Emmanuele Severi, Nathalie Juge and Gavin H. Thomas The range of microbial uses of sialic acid.

Modelling virus infections of the 66 skin in 3D Sally Roberts and Joanna Parish Understanding infection through the use of organotypic raft cultures.

Human noroviruses and gut bacteria: 70 friends, frenemies or both? Matthew D. Moore Advancements and future directions in norovirus research.

The intestinal microbiota in health 74 and disease Katharine Seton and Simon R. Carding The role of the microbiome in human health. 46:2 May 2019 Features Regulars 57 Elinor P. Thompson, 49 Editorial Chair of the Eukaryotic Division 52 Council 2019 A Q&A with Elinor Thompson. 53 From the President 82 Grants 54 From the Chief Executive Spotlight on Harry Smith Vacation Studentships. 55 News 78 Annual Conference 2019 and 2020 83 Career Focus – Putting together your CV 80 Focused Meetings 2019 A summary of the topics covered in the CV workshop at Annual Conference 2019. 94 Reviews 84 Open research: it’s more than open access Editor Rowena Jenkins Open science and fair data. Managing Editor Ruth Paget Production Editor Ellen Hinkley 86 The Global Sustainability Development Editorial Board Andre Antunes, Nigel Brown, David Blackbourn, Rachel Exley, Lorena Fernández-Martínez, Rebecca Hall, Freya Harrison, Chloe James, Report on the Sustainable Development Goals Chris Randall, Nicola Stonehouse Microbiology and the Global Sustainability Developement Report. Address Microbiology Society, Charles Darwin House, 12 Roger Street, London WC1N 2JU T +44 (0)20 7685 2683 E [email protected] 88 Championing Microbiology and the Design Ian Atherton, Corbicula Design (www.corbiculadesign.co.uk) Printed by Charlesworth Press, Wakefield Microbiology Society © 2019 Microbiology Society Find more about being a Society Champion. ISSN 1464-0570 The views expressed by contributors do not necessarily reflect official policy of the Society; nor can 91 ECM Forum update – the claims of advertisers be guaranteed. Communications, conferences and careers FSC Logo Annual Conference, ECM Forum Summer Conference and elections. 92 Membership Q&A Gerard Sheehan from Maynooth University, Ireland. Faecal bacteria. Scanning electron micrograph of bacteria cultured 95 Comment – from a sample of human faeces. Fungal interactions in health and disease Magnification: x6000 when printed Courtney Kousser, Farhana Alam and Rebecca Hall 10 cm wide. Steve Gschmeissner/ Fungi and their interactions within the human microbiome. Science Photo Library Council 2019

Executive Officers President – Professor Judith Armitage Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU; [email protected] General Secretary – Professor Maggie Smith Department of Biology, Wentworth Way, University of York, York YO10 5DD; [email protected] Treasurer – Professor Ian Roberts School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, Michael Smith Building, University of Manchester, Manchester M13 9PT; [email protected]

Chairs of Committees Communications Committee – Professor Nicola Stonehouse School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT; [email protected] Early Career Microbiologists’ Forum Executive Committee – Amy Richards The Roslin Institute, Easter Bush Campus, Edinburgh, Midlothian EH25 9RG; [email protected] Finance and Operations Committee – Professor Ian Roberts See ‘Treasurer’ above Policy Committee – Professor Paul Kellam Imperial College London, Faculty of Medicine, St Mary’s Campus, Norfolk Place, London W2 1PG; & Kymab Ltd; [email protected] Professional Development Committee – Dr Tadhg Ó Cróinín Health Science Centre, University College Dublin, Belfield, Dublin 4, Ireland;[email protected] Publishing Committee – Professor Jodi Lindsay Institute of Infection and Immunity, St George’s, University of London, Cranmer Terrace, London SW17 0RE; [email protected] Scientific Conferences Committee – Professor Mick Tuite School of Biosciences, University of Kent, Canterbury CT2 7NJ; [email protected]

Elected Members Professor David J. Blackbourn The School of Biosciences and Medicine, 14 AX 01, Edward Jenner Building, Faculty of Health & Medical Sciences, University of Surrey, Guildford, Surrey GU2 7XH; [email protected] Professor Deirdre Devine School of Dentistry, University of Leeds, St. James’ University Hospital, Leeds LS9 7TF; [email protected] Professor Charles Dorman Department of Microbiology, Moyne Institute of Preventive Medicine, Trinity College Dublin, Dublin 2, Ireland; [email protected] Dr John Morrissey School of Microbiology, University College Cork, Ireland; [email protected] Professor Tracy Palmer Centre for Bacterial Cell Biology, Baddiley-Clark Building, Medical School, Newcastle University, Newcastle upon Tyne NE2 4AX; [email protected] Professor George Salmond Department of Biochemistry, Hopkins Building, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW; [email protected]

52 Microbiology Today May 19 | microbiologysociety.org From the President

The Microbiology Society’s 75th anniversary activities for 2020 are gaining momentum. You may be aware of the recently launched United Nations Sustainable Development Goals (UN SDGs) project, A Sustainable Future, and our call for evidence. We are seeking your views to find out how microbiology can and does contribute to achieving the UN SDGs. We would welcome your input and response to this ambitious project to showcase the impact of microbiology and how it relates to the 17 goals that will transform our world. The questionnaire can be found on the Microbiology Society website microbiologysociety.org/SDGs.

s part of the 75th anniversary The Focused Meeting series for Microbiology, which will publish replication celebrations we will be extending 2019 begins in June with two events, studies, negative or null results, research Athe Annual Conference in 2020 one on anaerobes and the second on proposals, data management plans, so it runs over five days, with the first yeasts. You can find out more about additional research methods and day showcasing our Fleming Prize these events and three further Focused interdisciplinary work. Articles published winners. This event will outline a vision Meetings taking place later in the year are free to read and currently free to for the future impact of microbiology on on pages 80–81. Another key event in publish, as article processing charges science and society and will reflect on the Society calendar is the Early Career are waived at the current time. some of the science that outstanding Microbiologists’ (ECM) Forum Summer I will soon be stepping away from microbiologists, at all career stages, Conference 2019, taking place in Dublin publishing research articles and running a are involved in to overcome global on 21–22 June. The Society is keen to lab to focus more on my role at the Society challenges. More information on the create a supportive environment for those and a range of other commitments. On programme will be announced on starting out in their career, with peer-led reflection, looking back at my career to our website later in the year. sessions to help enhance the professional date, I see that the key milestones and I enjoyed my first Annual development of researchers. If you are points where I have forged ahead were Conference as President of the an early career researcher, it is a great built on collaboration, adaption and the Microbiology Society and attending opportunity to build networks and willingness to search for answers when talks on the range of microbial science develop your skillset. I was uncertain of the outcome. As we the Conference celebrates. I was truly When presenting work, there is also face changes such as AMR, opportunities inspired by the work of my fellow the consideration of publishing your in genome research and an increasing microbiologists and am keen to find research. The publishing landscape has understanding of the importance of out more about the work taking place changed significantly in the last decade microbial communities, I continue to be across the UK and Ireland. I hope to meet and continues to change, with a range of amazed by the microbial world and its you at one of the upcoming Roadshow terminology and different ways to publish key role in our continued existence. I am events, taking place in Dublin, Plymouth, that we all need to be aware of. To the determined to champion the field and Manchester and Liverpool in Autumn. uninitiated it can be difficult to navigate. help ensure microbiology is firmly on the I was really heartened by the warm Our Journals Team can help your agenda, helping support you in finding welcome I received at the Leeds and understanding of the process with an the answers to some of the significant Newcastle Roadshow events in March. article on pages 84–85 on Open Access, challenges our community faces. I enjoyed meeting members at these outlining how this works. events and finding out more, not only The Microbiology Society journals Judith Armitage about their research but also their provide the microbiology community with President concerns for the future and possible a place to publish their findings. This now [email protected] ways in which the Society might help. also includes our new journal, Access

Microbiology Today May 19 | microbiologysociety.org 53 From the Chief Executive

In the past few months, two events have very powerfully shown the value of a membership charity like the Microbiology Society in supporting members. Back in March, our new President, Judith Armitage, began her members’ Roadshow by visiting Leeds and Newcastle, where we met a large number of members to learn more about how the Society can support your career progression. Then, last month the Annual Conference was a festival of microbiology and friendship where over 1,300 researchers came together to share results, make new connections and renew existing ones.

t the Roadshow events, Judy and one from Nobel Laureate Paul Nurse, will look at the journey from discovery to described her own career who won the Fleming Prize in 1984. There the impact of research. The International Apath, and the thing that clearly will be inspiring talks, ranging from ‘The Meeting on Arboviruses and their Vectors, struck a chord with many early career expanding virosphere’ by Eddie Holmes, being held in Glasgow in September, members was that Judy’s success has one of the world’s leading experts on virus is now an established and unmissable not always been plain sailing. Everyone evolution, through to Mark Pallen of the meeting that Alain Kohl regularly faces significant challenges in a research Quadram Institute, talking about ‘What organises with colleagues. career. Judy’s advice was clear – find a ancient DNA can tell us about pathogens October will see a special meeting scientific question that fascinates you from the past’. in Dublin organised by Joan Geoghegan and keep working at it even if it’s not But as well as established experts, and Charles Dorman. The Irish Division fashionable, and build a strong support there will be a platform for early career will celebrate a century of microbiology network of collaborators. microbiologists, including a number of at Trinity College Dublin with a meeting Of course, one of the most effective ‘Five-Minute Theses’, where PhD students on Microbes in Medicine. Charles is ways of doing this is to attend the will present their results to the Society’s Professor of Microbiology at Trinity; he is Society’s Annual Conference, and this membership. We will learn more about also a member of Council and he won the year’s event in Belfast was a brilliant the career paths of some of the Fleming Fleming Prize Lecture in 1994, underlying example. As we do every year, we brought Prize winners, where the winners the long-established links between the together scientists interested in microbes, will outline what went well and what Society and microbiology in Ireland. The their effects and their practical uses, and challenges they met along the way. Many last Focused Meeting of the year will be created as many opportunities as we of the Fleming Prize winners already have in Oxford at the end of October, where could to get you talking to one another the date of next year’s anniversary Annual Freya Harrison and colleagues will focus about your science, the challenges you Conference in their diaries, 30 March to 3 on antimicrobial drug discovery from face and your careers. April 2020 in Edinburgh, and I can’t wait to traditional and historic medicine. Finally, If it’s possible, next year’s Annual see so much microbiological talent in the in November, we are delighted to host Conference is going to be even better. same room and at the same time. the Federation of Infection Societies (FIS) 2020 will be the 75th anniversary of In the meantime, this year has an Annual Conference in Edinburgh. the Microbiology Society, and one of the exceptional series of Focused Meetings, There is something for everyone in ways we will celebrate is by adding an starting with Anaerobe 2019 in Cardiff the programme and I hope to see you at extra day to the Conference, organised in June, organised by Sheila Patrick and one of the meetings. by former winners of the Fleming Prize colleagues, which will look at changing Lecture. The programme will include perceptions of anaerobic bacteria. Peter Cotgreave two keynote lectures – one from Bonnie Later the same month, Janet Quinn and Chief Executive Bassler, famous for her pivotal role in the colleagues are organising the British [email protected] discovery of quorum sensing in bacteria, Yeast Group meeting in Newcastle, which

54 Microbiology Today May 19 | microbiologysociety.org Get the latest updates, search for the Microbiology News Society on:

@MicrobioSoc

Nominate a deserving microbiologist Focused Meeting 2020 proposals for a Microbiology Society Prize Lecture Focused Meetings incorporate presentations from leading scientists with opportunities for those new to the field Nominations for the Prize Lectures 2020 and Prize Medal to present their research via offered talks and poster 2021 close on 10 June 2019, and are welcomed from all members. If you know a researcher whose work is presentations. Applications to organise a Focused Meeting deserving of recognition, nominate them on our website are invited from any field of microbiology and can be based around an established community, a hot topic or an emerging (microbiologysociety.org/prizelectures). The Society is committed to creating and encouraging a diverse and one. Information, including previous events, is on our website inclusive culture within our membership and the microbiology (microbiologysociety.org/focusedmeetingproposals). Send community. Please consider the full breadth of the field when your proposal by 10 June 2019 for consideration by our making your nomination. Scientific Conferences Committee. Access Microbiology – first articles online Funding for local events The Microbiology Society’s newest journal, Access Did you know that members of the Early Career Microbiology, has published its first articles.Access Microbiologists’ (ECM) Forum have access to a special fund for Microbiology introduces a new service to members of their own events? Apply online for up to £500 to support local our community, allowing the publication of replication events that bring ECMs together. studies, negative or null results, research proposals, data management plans, additions to established methods, Membership subscription rates and interdisciplinary work. To find out more about the The Society is looking to align its membership subscription journal, or to read the latest articles, visit our website rates to ensure they comply with current legislation. We will (acmi.microbiologyresearch.org). no longer be offering reduced rates for members who elect to pay by direct debit. In future, all members will pay the Society-Supported Conference Grants 2020 same rates for their grade of membership, irrespective of Members who are planning to organise a conference can the way they choose to pay. We will be communicating the apply for a grant of up to £2,000 towards funding the costs new rates soon. If you have any queries, please contact of invited speakers. Awards for 2019 meetings have been [email protected]. allocated, but applications are now welcome for meetings in 2020. Visit microbiologysociety.org/SSConferencegrants for Grant deadlines details. Date Grant FIS 2019 1 June 2019 Travel Grants to support members presenting at conferences or attending The Microbiology Society is proud to be hosting the training courses from 1 July to Federation of Infection Societies (FIS) Conference 2019 30 September. this November at the EICC in Edinburgh, UK. Visit microbiologysociety.org/FIS19 to see what’s in store this year Various dates Society Conference Grants to attend a and submit an abstract to be part of this event. Registration Focused Meeting this summer. opens in early June and abstracts will close on 5 August 2019. For more information please visit the website Follow us on Twitter @MicrobioSoc, using the hashtag #FIS19. microbiologysociety.org/grants.

Microbiology Today May 19 | microbiologysociety.org 55 56 Microbiology Today May 19 | microbiologysociety.org Elinor P. Thompson Chair of the Eukaryotic Division

The Society has four Divisions (Eukaryotic, Prokaryotic, Virology and Irish) which consist of Society members who support the organisation and plan sessions and symposia for the Society’s events programme. Each Division Chair and Chair-Elect sit on the Scientific Conferences Committee and the Chair reports into the Society’s governing body, Council. In this article we introduce Elinor Thompson, Chair of the Eukaryotic Division. She tells us about her

background and her role on the Division. Elinor Thompson

am a Senior Lecturer at the and Mr Smith – the former lent me I have been involved in organising University of Greenwich and my and my friend the school telescope to sessions for the conferences for a Iresearch is mostly on families of take home at weekends, and the latter few years, trying to think of subjects membrane proteases involved in did a whole course in microbiology and speakers who will attract a good signalling and regulation, in a range as part of our Biology A level. I am on audience at the Annual Conference. The of model organisms – my work on the video somewhere demonstrating sub- admin for this is deciding session order, social amoeba and model eukaryote culturing at the age of 16! I did work as evaluating offered talks and posters Dictyostelium is the reason I became a scientific writer and editor for a while for sessions, and the Chair keeps an involved with the Eukaryotic Division. after graduating, though, until I was sure eye on all the sessions. The nicest jobs My lab has a longstanding interest I wanted to do a PhD. are meeting up as a Division to discuss in organelle function too, and our progress, attending the Conference, molecular biology resources mean we When did you join the Microbiology of course, and the extras such as are drafted in to help with a whole range Society and why did you join? judging the Sir Howard Dalton Young of biology or medical projects. I worked at the Society on the Journal Microbiology of the Year Competition of General Virology when I graduated, (which is always humbling in the quality When did you first decide you to take a break from academic life, of the talks). wanted to do science (and why)? so I knew about the Society from that I thought about this when I was applying point, and joined as soon as I went to What motivated you to be part to study microbiology at university. The University College London to do an MSc of the Division? interviewers’ questions at University then PhD. I started scientific life as a microbiologist College London made me realise that and had been a member of the Society scientific, or at least technical and Please describe your role on the for a long time. My students and I have medical, thoughts had always been Division. benefitted from Microbiology Society around me. One of my grandmothers I was a Division member and Chair support and I am honoured to have been was a midwife and health visitor, the Elect before taking over as Chair, so able to return the favour. other was a pharmacist, and my father Are you a member and would you like to join one of the Divisions? Find out is an engineer. I also grew up in the more about the Divisions and what they do on our website (microbiologysociety. deepest, nowhere countryside with org/divisions). The Council and Committees shadowing scheme is also a lots of nature around. As with so many fantastic opportunity to gain an insight into the work of the Society and gain scientists, the most important people first-hand experience of our Council and Committee activities. Find out more on were probably my secondary- and the Society website: microbiologysociety.org/shadowingscheme. high-school science teachers, Mr Cross

Microbiology Today May 19 | microbiologysociety.org 57 Where bacterial metabolism and virulence intersect

Coloured scanning electron micrograph of Pseudomonas aeruginosa bacteria (blue) Kim R. Hardie on ciliated human nasal epithelium. Juergen Berger/Science Photo Library

58 Microbiology Today May 19 | microbiologysociety.org of Serratia marcescens. Unlike AI-2, ‘We are what we eat’, and so are the bacteria that live on other QS signal molecules (QSSMs) us. If bacteria do not have the building blocks or metabolic do not feed back into metabolism as directly, but are produced by dedicated pathways and capacity to create their healthy cell, they will synthases, with the goal of interacting with cognate regulators, e.g. N-acyl be disadvantaged when it comes to establishing an infection. homoserine lactones (AHLs) and alkyl quinolones (AQs). QS dictates that QSSMs accumulate, thus their production is a or example, an incomplete ways, virulence and metabolism are drain on the metabolic pathways that peptidoglycan or intimately linked, and this feeds into are specific to the generation of the Flipopolysaccharide (in Gram- the ‘survival of the fittest’ theories of substrates from which they originate. negative bacteria) would leave them evolution. The feeder metabolic pathways include weakened and more susceptible to amino acid and fatty acid synthesis, and harsh environments, the immune Metabolic pathways can be when depleted there is a fitness burden system or antimicrobials. Metabolism co-opted as a virulence strategy that impacts upon virulence. This impact provides these building blocks, thereby LuxS is a metabolic enzyme, central to is serious enough for cheating bacteria contributing to pathogenicity via boosting the activated methyl cycle that converts (QS responders that do not make QSSMs) cell fitness. Metabolism also generates S-ribosyl homocysteine to homocysteine, to exist in populations. the substrates (amino acids, sugars, etc.) releasing 4,5-dihydroxy-2,3-pentadione for virulence factors (which are defined (DPD). DPD cyclises spontaneously Balancing the cost of virulence as macromolecules that contribute to to generate autoinducer 2 (AI-2), that and metabolism breeds population infection severity). can serve as a temporally-released diversity which ultimately fuels metabolite. Some bacteria do solely pathogenicity Scavenging for nutrients to this, and uptake AI-2 in times of need Not every bacterium plays fairly, leading feed metabolism boosts virulence to feed it back into metabolism. When to heterogeneity in populations that It has long been known that bacteria luxS is disrupted, there is a reduction in enables bacteria to progress infections produce macromolecules to scavenge fitness which can affect pathogenicity, under adverse conditions, e.g. non- for key molecules required for for example, by curbing biofilm producing cheaters benefit from the metabolism, such as iron. If acquisition formation. Other bacteria have been production of virulence factors made or utilisation of these resources is able to exploit the AI-2 to count their by other bacteria, but have a reserve in impaired, so is their pathogenicity. This population size, and use it to trigger a their metabolic bank if environmental may be linked to survival in a certain specific regulatory response when the conditions change. Likewise, relatively niche, e.g. blood, or to accomplish a population density reaches a critical metabolically inert cells, such as key stage in infection: for example, size: i.e. quorum sensing (QS). If the QS persisters, are maintained to enable biofilm formation. Similarly, regulators regulon encompasses virulence factors, survival when slow growth is an integrated into nutrient acquisition pathogenicity will be affected directly. advantage, where nutrients are scarce, also control virulence factors, such as for example, such as in the depths of the sigma factor linked to metabolism Virulence factor production a biofilm, or during the onslaught of of nitrogen, RpoN or Fur (the ferric drains metabolic pathways antimicrobials. uptake regulator). Conversely, virulence On the opposite side of the coin, the regulators also exert regulatory control production of virulence factors draws Bacteria share metabolic over metabolic pathways, e.g. EfpR in the on metabolism, and this fitness cost resources to establish an infection plant pathogen Ralstonia solonacearum can impair pathogenicity. For example, Some pathogens have evolved to make or regulators encoded on the Salmonella capsule production and glucose the best of heterogeneous metabolisms pathogenicity island 13 (SP-13). In these metabolism collide in dictating virulence in a population by cross-feeding. Cross-

Microbiology Today May 19 | microbiologysociety.org 59 feeding is evident within the complex raffinose may be the ultimate biofilm communities of plaque in the determinant controlling whether a oral cavity where Streptococcus gondii S. pneumoniae infection is established depends on the keystone pathogen in the blood or the ear, with clinical Porphyromonas ginivalis generating isolates from the blood utilising 4-aminobenzoate/para-amino benzoic raffinose more efficiently. Interestingly, acid (pABA) for folate biosynthesis. this highlights how differential Marvin Whiteley’s group demonstrated carbohydrate metabolism not only this co-dependence extended beyond alters virulence, but can even impact nutrient provision to the promotion of on the disease caused. Whether the respiratory growth of a pathogen by a underlying mechanism of the raffinose commensal that enhanced virulence. uptake is linked directly to metabolic This is likely to have implications in status of the bacteria is not entirely polymicrobial infections such as those clear. It is possible that different host found in wounds. niches have altered sugar availability which influences the need to metabolise Virulence factors can generate raffinose and gain a fitness advantage. a new metabolic resource It is also possible that depleting the Some virulence factors can provide raffinose concentration may alter nutrients that provide a fitness aggregation and biofilm potential as Serratia marcescens. Sinhyu/iStock advantage. For example, the surface- a virulence strategy. tethered aminopeptidase autotransporter during an infection a virulence factor? of Pseudomonas aeruginosa, AaaA, can A metabolic pathogenic Is a virulence factor that provides generate arginine locally that can be strategy that disadvantages a metabolite better defined as a metabolised by the bacteria, and could the microflora metabolic pathway component? Current be a strategy to survive in environments Salmonella Typhimurium uses one technology platforms are developing with limited oxygen, such as within a pathogenicity island (SPI-1) to encode fast, and ultimately we will be able to biofilm microcolony. a type 3 secretion system (T3SS- analyse the metabolome and virulence 1) to promote inflammation in the factors simultaneously in single cells A metabolic switch can turn intestinal tract. The inflammation in a population. This may perhaps be a commensal into a pathogen initiates production of tetrathionate and possible in real time using secondary The nasopharyngeal commensal ethanolamine which can be utilised ion mass spectrometry (SIMS) imaging Streptococcus pneumoniae colonises by the S. Typhimurium to trigger rapid such as ORBI-SIMS and Nano-SIMS, and 65% of individuals. Bacteria from expansion of the pathogen at the Raman coupled to confocal microscopy this reservoir can invade the lungs expense of the commensals. or fluorescence in situ hybridisation to cause pneumonia, the blood to (FISH) which will help us decipher these cause bacteremia, the central nervous Concluding perspectives conundrums. system to cause meningitis or ascend The interplay between virulence and the eustachian tube to the middle metabolism is complex, and searching Further reading ear and cause otitis media. Virulence the literature for relevant information Anderson MT, Mitchell LA, Zhao L, factor switches, for capsule serotype is plagued by non-specific terms. Mobley HLT. Capsule production and for example, contribute to infection However, it is apparent that the two are glucose metabolism dictate fitness during progression by enabling pathogens linked, although it is difficult to define Serratia marcescens bacteremia. Proteomics to survive in different niches. Minhas et the boundaries between the two. Is 2017;17:23–24. al. reported that altering uptake a metabolic enzyme/regulator that Davis KM, Isberg RR. One for All, but Not All and utilisation of the trisaccharide provides a cell with a fitness advantage for One: Social Behavior during Bacterial

60 Microbiology Today May 19 | microbiologysociety.org for Pseudomonas aeruginosa mediated by a virulence regulatory network promotes an autotransporter with arginine-specific robustness in a plant pathogen. Nat Commun aminopeptidase activity. PLoS Pathog 2018;9:418. 2012;8:e1002854. Robinson AE, Heffernan JR, Henderson JP. Minhas V, Harvey RM, McAllister LJ, The iron hand of uropathogenic Escherichia Seemann T, Syme AE et al. Capacity to utilize coli: the role of transition metal control in raffinose dictates pneumococcal disease virulence. Future Microbiol 2018;13:745–756. phenotype. MBio 2019;10:e02596-18. Ruparell A, Dubern JF, Ortori C, Harrison F, Perrier A, Peyraud R, Rengel D, Barlet X, Halliday N et al. The fitness burdens imposed Lucasson E et al. Enhanced in planta fitness by synthesising quorum sensing systems. Nat through adaptive mutations in EfpR, a dual Sci Rep 2016;6:33101. regulator of virulence and metabolic functions Stacy A, Fleming D, Lamont RJ, in the plant pathogen Ralstonia solanacearum. Rumbaugh KP, Whiteley M. A commensal PLoS Pathog 2018;12:e1006044. bacterium promotes virulence of an Peyraud R, Cottret L, Marmiesse L, opportunistic pathogen via cross-respiration. Genin S. Control of primary metabolism by MBio 2016;7:e00782-16. Kim R. Hardie Centre for Biomolecular Sciences, School of Life Sciences, University of Nottingham, University Park, Serratia marcescens. Sinhyu/iStock Nottingham NG7 2RD, UK e [email protected] Diseases. Trends Microbiol 2019;27:64–74. Elder JR, Paul NC, Burin R, Guard J, Shah Kim Hardie studied for a BSc in Biological Sciences, DH. Genomic organization and role of SPI-13 before completing a PhD investigating Escherichia coli in nutritional fitness of Salmonella. Int J Med Hardie Kim R. haemolysin. She has since worked in postdoctoral Microbiol 2018;308:1043–1052. positions at the University of Victoria, Canada, and the Institut Pasteur, Paris. Hardie KR, Heurlier K. Communication in Her research at the University of Nottingham has focused on autotransporters, bacterial communities: contribution of LuxS quorum sensing, biofilms and AMR complements, and she holds governance to biofilm development. Nat Rev. Microbiol roles within the Microbiology Society and Royal Society of Biology. 2008;6:635–643. Kalidasan V, Joseph N, Kumar S, Awang What does a typical week involve for you? Hamat R, Neela VK. Iron and Virulence in A typical week is working 8:00–18:00 on a mixture of research supervision Stenotrophomonas maltophilia: All We Know meetings, lectures and workshops for students. It also involves pastoral support So Far. Front Cell Infect Microbiol 2018;8:401. and mentoring, interactions with external academics and also far too much Kang D, Kirienko NV. (2018) Interdependence admin. Most evenings involve an hour or so on the computer and spending time between iron acquisition and biofilm with my two daughters and husband. For a treat, I cook something special, go to formation in Pseudomonas aeruginosa. J the gym, knit or read a novel. Most weeks involve at least one IT annoyance and if Microbiol 2018;56:449–457. I’m lucky there will be a trip somewhere to examine, plan research, hear science Kuboniwa M, Houser JR, Hendrickson or get involved with external governance. EL, Wang Q, Alghamdi SA et al. Metabolic What inspired you to become a microbiologist? crosstalk regulates Porphyromonas The fascination to understand how bacteria, which are so small and single-celled, gingivalis colonization and virulence during can do almost everything a whole organism can do. Microbiology is pure systems oral polymicrobial infection. Nat Microbiol biology without even trying, and the ideal component of multidisciplinary science. 2017;2:1493–1499. Most importantly, bacteria do not bleed, so they don’t make me squeamish, and Luckett JCA, Darch O, Watters C, AbuOun they are easier to grow than plants. M, Wright V et al. A novel virulence strategy

Microbiology Today May 19 | microbiologysociety.org 61 A special sugar: how sialic acid impacts on metabolism, health and disease

Andrew Bell, Emmanuele Severi, Nathalie Juge and Gavin H. Thomas Neu5Ac We are teeming with microbes that live on surfaces outside and OH OH inside our bodies. Our understanding of the gut microbiome in HO particular is rapidly improving as we start to unpick how complex O HO COO– AcHN microbial communities interact with our diet, with other microbes HO Neu5Gc and with our cell surfaces. While many chemicals are important OH in this milieu, here we focus on sialic acids as a critical set of HO OH HO molecules that underpin many of these interactions and impact on H O N COO– metabolism, health and disease. O HO he most common sialic acid, cell surfaces. Cell-surface or secreted HO N-acetyl-neuraminic acid (Neu5Ac) mucin glycoproteins are good examples (Fig. 1) is a relatively simple sugar of sialic acid-coated structures that 2,7-anhydro-Neu5Ac T acid that, apart from its charge, has microbes could encounter at mucosal HNAc nothing intrinsically unusual about it. surfaces, such as the respiratory or O However, when cells contact other cells gastrointestinal (GI) tract. This unique COO– they often use molecules displayed on position as the ‘meet and greet’ molecule the surface, and this is where sialic acids for other human cells, bacterial cells and HO O HO become so important, as they are usually viruses puts the sialic acids at centre- the terminal sugars on the host glycans stage for many important processes. HO that pepper proteins and lipids sitting on Sugar-coated pathogens Fig. 1. Example of sialic acid derivatives. Note that the N-glycolyl-neurnaminic acid (Neu5Gc) cannot be made One of the first microbial functions of by humans, a biochemical difference that distinguishes us from other great apes, but can be incorporated into sialic acids was connected to the ability our cell surfaces when acquired from the diet. Andrew Bell of some pathogens to colonise and then

62 Microbiology Today May 19 | microbiologysociety.org PATHOGENS COMMENSALS/OPPORTUNISTIC PATHOGENS Exploitation – (a) Scavenging to form ‘Invisibility Cloak’ (b) Feeding (c) Commensal cross-feeding (d) post-antibiotic treatment (e) Selfish consumption Resistance to complement- mediated killing HOST HEALTHY GUT DISEASE

SCFA E. coli S. typhimurium Growth Growth C. difficile Growth LPS LPS LPS LPS LPS Neisseria sp. V. cholerae B. thetaiotaomicron B. thetaiotaomicron R. gnavus H. influenzae Food Cross-feed Free food Food (Host) Free Sia Sialidase Sialidase Sialidase IT-Sialidase Sialidase

Gal GalNAc Glc GlcNAc Man Fuc Sia 2,7-anhydro-Neu5Ac

Fig. 2. Cartoon illustration of the various interactions between bacteria and sialic acids present as terminal sugars on a range of host glycans. These are cleaved by sialidases and usually converted to free Neu5Ac with the exception of the IT-sialidase that releases 2,7-anhydro-Neu5Ac. Free sialic acid released by host or pathogenic sialidases can then be used by pathogens as an invisibility cloak (a), or for feeding (b). Cross feeding can occur between members of the gut microbiota or between commensal and pathogenic bacteria sharing the same niche (c, d) while other bacteria have developed selfish mechanisms to reserve sialic acid for their own consumption (e). Emmanuele Severi cause disease in humans. Indeed, the pretty good food for bacteria, as sialidases to release the sialic acid but ex-President of the Microbiology Society, they provide both carbon and nitrogen, lack transporters and catabolic genes to Professor Harry Smith FRS, working at and can be used as an energy source. actually use it. This seemingly altruistic the University of Birmingham, pioneered Earlier work showed that pathogens gesture is required for the bacteria to this work with Neisseria gonorrhoea. such as Vibrio cholerae were happy access underlying sugars and underpins When scientists in his group isolated just to eat sialic acids and that in itself a process of metabolic cross-feeding the bug directly from the body, it was was important for successful host to other bugs living in the mucus niche, resistant to killing by human serum colonisation (Fig. 2b). like commensal Escherichia coli strains (complement-mediated killing), but if In the gut, a major source of that do not have a sialidase but are the bugs were cultured in the lab for a sialic acids comes from mucins, good at eating free sialic acid (Fig. 2c). few generations, this protection was lost which are the main structural This concept is now recognised as and the cells were killed by the serum. components of the mucus layer an important aspect of colonisation His group had discovered that these covering the epithelium surface. and niche adaptation. A brilliant pathogens steal sialic acid from the The most exposed layer of mucus is exemplification of this was described host and use it to coat their own cell the habitat of various commensal by the group of Justin Sonnenburg surface to humanise them. However, as bacteria, which have learnt how to from Stanford University, using a they can only scavenge this sialic acid, feast on mucin proteins, where sugars mouse model with a simple defined its absence in growth media means make 80% of their mass. From a gut microbiota. Following antibiotic no further sialic acid is added so they simple topological perspective, the treatment, many of the sialic-acid-eating rapidly lose this ‘serum protection’ and sialic acids, as the terminal sugars, are bacteria were wiped out, resulting in are killed. It turns out that a range of harvested first, exposing the underlying the accumulation of free sialic acid in other sneaky bugs use similar strategies sugars that can also be subsequently the gut. When then challenged with to generate their own invisibility cloak released and eaten. With the advent of pathogens like Salmonella typhimurium using sialic acid, such as Neisseria next-generation sequencing, we have or Clostridium difficile, these pathogens meningitidis, Campylobacter jejuni or gained knowledge on the microbes would benefit from the free sialic acid Haemophilus influenzae (Fig. 2a) living in this niche, and many have as a nutrient (Fig. 2d). Mutant strains genes for sialic acid uptake and of pathogens lacking the transporters Cross-feeding – subsequent catabolism. What was or catabolic genes did not have an sharing the sweets around exciting was the discovery that some advantage, making a direct connection As well as being used by pathogens of the commensal anaerobes, like to pathogen outgrowth when the gut as an invisibility cloak, sialic acids are Bacteroides thetaiotaomicron, secrete microbial community is disrupted.

Microbiology Today May 19 | microbiologysociety.org 63 H3N2 influenza virus particles. CDC / Science Photo Library Mechanisms to reduce the pool of free Viruses get in on the act sialic acid in the gut were therefore Viruses also use sialic acids as key molecules during their infection cycle, most proposed as part of a novel anti- famously influenza virus. Initial attachment is the first key step as sialic acids infective strategy. function as the receptors for the virus on respiratory epithelial cells. The type of linkage of the sialic acid to underlying sugars in the glycans often controls the Keeping hold of your own host range of influenza viruses, and pandemic strains often have adhesion protein sweets (hemagglutinin) that recognises the human-like forms of sialic acid attachment and While much early sialomicrobiology so are particular virulent. Sialic acid is important at the last stage in the viral life focused on pathogens, more recent cycle as release from the infected cell requires cleavage of sialic acids off the host work has focused on the commensal cell surface. This is catalysed by a viral enzyme called sialidase (or neuraminidase). bacteria inhabiting the same niche. Inhibition of this enzyme by structural analogues of sialic acid, formulated into Today’s studies in the field of the gut Tamiflu® (Oseltamivir phosphate) and Zanamivir, are our front-line treatment for microbiota are revealing how fierce influenza and are a triumph of structure/function inspired drug design. the competition for Neu5Ac is in our gut and how it can tip the balance colonisation within the mucus mammalian cell surfaces. In this between pathogens and commensals. layer. Once located in the right place, short article, we have touched on What if a particular bacterium could the IT-sialidase cleaves off sialic some of these to give an idea of the release sialic acid in a form that acid from the terminal chains of central functions of these sugars in only it could access? Work in the mucins and releases it in a form, communication, stealth, colonisation Juge Group in Norwich showed that 2,7-anhydro-Neu5Ac, that R. gnavus and metabolism in different aspects the gut symbiont Ruminococcus gnavus can use as its own source of food, of heath and disease. Sialic acids has evolved to do so, using a special rather than sharing Neu5Ac with have been described as the most type of sialidase called an intramolecular other bacteria inhabiting the mucus important chemicals in the world trans-sialidase (IT-sialidase) which niche, including pathogens (Fig. 2e). and will no doubt continue to reveal releases 2,7-anhydro-Neu5Ac This mechanism provides a competitive more about the evolution of humans (see Fig. 1) instead of Neu5Ac. By advantage over other sialic-acid- and their interplay with their developing a method to synthesise pure eating bacteria inhabiting the microbes. 2,7-anhydro-Neu5Ac, they showed that mucus niche, by providing a source of R. gnavus strains were able to grow nutrient that it can preferentially Further reading on 2,7-anhydro-Neu5Ac as the sole access. In addition, R. gnavus may Thomas, GH. Sialic acid acquisition in bacteria carbon source. In addition to the domain also help reduce outgrowth of enteric – one substrate, many transporters. Biochem catalysing the enzymatic reaction, pathogens by reducing the level of Soc Trans 2016;44:760–765. IT-sialidases comprise a carbohydrate Neu5Ac in the mucosal environment, Ng KM, Ferreyra JA, Higginbottom SK, binding domain which helps to mediate opening ways to a novel therapeutic Lynch JB, Kashyap PC et al. Microbiota- the binding of the IT-sialidase to sialic strategy in an age of increasing liberated host sugars facilitate post-antibiotic acid rich mucins. In vivo, this may antibiotic resistance. expansion of enteric pathogens. Nature favour a mechanism that helps In conclusion, it is clear that 2013;502:96–99. targeting the bacteria towards sialic sialic acids are critical molecules in Owen CD, Tailford LE, Monaco S, Šuligoj T, acid rich regions of the GI tract, many processes where microbial Vaux L et al. Unravelling the specificity and therefore promoting bacterial cells and viruses interact with mechanism of sialic acid recognition by

64 Microbiology Today May 19 | microbiologysociety.org the gut symbiont Ruminococcus gnavus. Nat WM, Taylor GL, Juge N. Discovery of 2015;6:7624. Commun 2017;8:2196. intramolecular trans-sialidases in human Juge N, Tailford L, Owen CD. Sialidases from Tailford LE, Owen CD, Walshaw J, Crost gut microbiota suggests novel mechanisms gut bacteria: a mini-review. Biochem Soc EH, Hardy-Goddard J, Le Gall G, de Vos of mucosal adaptation. Nat Commun Trans 2016;44:166–175.

Andrew Bell Emmanuele Severi Quadram Institute Bioscience, Department of Biology, University Norwich Research Park, NR4 7UQ, of York, Wentworth Way, York UK YO10 5DD, UK e [email protected] e [email protected] Andrew Bell is a post graduate @emm_severi student in the Department Emmanuele Severi is a post- Emmanuele Severi Andrew Bell Andrew Gut Microbes and Health at doctoral research associate in the the Quadram Institute studying the impact of a novel Department of Biology at the University of York working mechanism of sialic acid metabolism on gut homeostasis. in the laboratory of Prof Gavin Thomas. He has worked on He obtained his BSc in Biochemistry from the University of sialic acid transport and metabolism at different times in East Anglia and spent 2 years working at the John Innes his career, and has been a member of the Society since Centre on chlorophyll metabolism in pea (Pisum sativum) 2002. before joining Nathalie Juge’s group at the Quadram Institute in 2015 for his doctoral work. Gavin H. Thomas Department of Biology, University Nathalie Juge of York, Wentworth Way, York Quadram Institute Bioscience, YO10 5DD, UK Norwich Research Park, NR4 7UQ, e [email protected] UK @GavinHThomas e [email protected] Gavin H. Thomas is a Prof. of Nathalie Juge is a Research Thomas Gavin H. Microbiology in the Department Leader at the Quadram Institute of Biology at the University of York and have worked on

Nathalie Juge Bioscience (QIB) in Norwich, Deputy bacterial sialic acid transport and catabolism for over a Leader of the Institute Strategic Programme, the Gut decade. He has been a member of the Society since 1995, Microbes and Health (GMH), and Honorary Professor at the was Editor of Microbiology Today (2003–2006), serving on School of Biological Sciences, University of East Anglia. Council in the same period, served on Communications She leads a Research Group on the glycobiology of host- committee (2012–2015) and the Equality & Diversity microbe interactions in the gut with a focus on mucin- committee (2013–2015). He has been an Editor, Senior Editor derived sialic acid metabolism by the gut microbiota and is now Deputy Editor-in-Chief of the Society’s leading (https://quadram.ac.uk/nathalie-juge). journal Microbiology (http://thomaslabyork.weebly.com).

Why does microbiology matter? Gavin: It matters for our health – only now are we really starting to understand the molecular composition and function of our microbiome, which likely impacts on our body in multitudinous ways. What advice would you give to someone starting out in this field? Gavin: Read widely and beyond ‘your bug’ – microbes can do pretty much everything and have usually invented multiple different ways to do it!

Microbiology Today May 19 | microbiologysociety.org 65 Modelling virus infections of the skin in 3D

Sally Roberts and Joanna Parish Using organotypic raft cultures to study the replication cycle of epithelial tropic viruses has given us revealing insights into the infection strategies and pathogenesis of clinically important viruses.

hen we think of skin, we The lower layer of the epithelium The underneath of the epithelium usually have in mind the is referred to as the ‘basal’ cell layer is separated from the dermis, which Wskin covering the outside and contains proliferating cells, harbours specialised structures such of our bodies, but our body cavities including self-renewing stem cells, as hair follicles, sweat and sebaceous (e.g. anogenital tract, oesophagus) whereas the upper or ‘suprabasal’ glands, and nerve endings by the and some organs (e.g. tonsil) are also layers are made up of differentiating basal lamina – a highly specialised lined by skin or to be more precise – cells (Fig. 1). Keratinocytes are the extracellular matrix structure. stratified squamous epithelium. Made major constituent cells of squamous Nourishment of the epithelium comes up of multiple layers and constantly epithelium, but other cell types from the basal side by diffusion renewed throughout our lives, through present include local antigen-presenting of nutrients and factors from the a tightly regulated balance between cell Langerhans cells and γδ T cells, underlying dermis. At the onset of proliferation and cell differentiation, our both involved in immunological differentiation, the basal cells become squamous epithelium performs many surveillance, mechanoreceptor Merkel detached from the basal lamina, stop functions, but one of its major roles is cells, and melanocytes which give proliferating and begin differentiation. to act as a barrier to micro-organism pigmentation and act to block UV As they travel upwards they become invasion. irradiation. more differentiated until in skin they

66 Microbiology Today May 19 | microbiologysociety.org Keratinised squamous epithelium Non-keratinised squamous epithelium Superficial Stratum keratinocytes corneum Keratohyalin granule Granular Langerhans cell layer Intermediate Keratinocyte keratinocytes Melanocyte Spinous Differentiation Stem cell layer

Merkel cell Sensory neuron Basal Basal layer keratinocytes Basal lamina

Dermis Dermis

Fig. 1. Structure of squamous epithelium – keratinising (left) and non-keratinising (right). S. Roberts, University of Birmingham (left); licensed under Creative Commons CCO 1.0 Universal Public Domain Dedication (right) form a keratinised, highly differentiated culture medium (Fig. 2). The collagen and an example is MCPyV which causes layer that is continually sloughed off, or plug is embedded with fibroblasts aggressive and often lethal Merkel cell in ‘wet’ mucosa (e.g. the uterine cervix), (isolated from dermis or a mouse carcinoma (MCC), which are located a non-keratinised superficial layer – fibroblast cell line) and acts as a dermal in the basal layer of epithelia. Dermal this process takes about two weeks to equivalent mimicking to some degree fibroblasts have been shown to support complete (Fig. 1). the mesenchymal–epithelial interactions productive MCPyV replication and are that occur in vivo. After about two therefore proposed as the target cell, Growing skin in the laboratory – weeks in organotypic raft culture the although no viral DNA has been detected organotypic raft cultures keratinocytes have formed into 3D in the dermis adjacent to virus-positive Recapitulating the complex process of structures of full thickness and fully MCC – the debate is ongoing. epithelial differentiation in a laboratory differentiated epithelium, and accurately as a way of making ‘skin’ for treating mimic the physiology of squamous Herpesvirus replication in 3D burns was the ‘Holy Grail’ in skin epithelium. The alphaherpesviruses varicella zoster research for many decades. One of the virus (VSV), which causes chicken pox, most important discoveries was being Viruses that replicate in the skin and the herpes simplex viruses (HSV) 1 able to isolate and grow keratinocytes Even though the epithelium is a and 2 associated with oral and genital from skin on a feeder layer of mouse barrier to infection, a number of herpes, enter the host via infection of fibroblasts for several successive clinically important viruses replicate the differentiating squamous epithelial generations – the next big step was in our epithelia including both alpha- cells and subsequently establish lifelong to get them to differentiate to form a and gammaherpesviruses, human latency in the dorsal root ganglions. physiological replica of the epithelium. papillomaviruses (HPV), Merkel cell Reactivation of these viruses (VSV – Since squamous epithelia are surface polyomavirus (MCPyV), and poxviruses. shingles, HSV – recurrent genital herpes) tissues with their upper regions exposed Notably, many of these viruses have can be problematic for the host and a to the outer/inner environment and been designated by the World Health high burden on healthcare facilities. nourished from the basal side, the Organization as carcinogens because Primary skin keratinocytes infected with isolated keratinocytes are grown on infections are at risk of developing virus following lifting to the air–liquid a plug of collagen (a scaffold) and the into cancer. For some viruses the interface in organotypic raft culture structure lifted to the air–medium keratinocyte is the target cell for their supported replication and spread of surface supported by a metal grid or cell replication cycle, but skin keratinocytes these viruses. The 3D models have been culture plastic insert (although originally might also act as the entry portal of used as a platform for screening of the collagen plugs were floated on the various pathogenic arboviruses following antivirals and several compounds that media surface, probably leading to the a mosquito bite. For others there is reduced replication and spread of ‘raft’ terminology), so that the underside some uncertainty surrounding the these alphaherpesviruses have been of the plug is in contact with the tissue nature of target cells in the epithelium, identified.

Microbiology Today May 19 | microbiologysociety.org 67 Squamous epithelium Infectious virus Tissue equivalent Viral genome culture dish Solid Collagen-embedded support fibroblasts

Growth medium

Fig. 2. Organotypic raft culture. S. Roberts, University of Birmingham

The gammaherpesvirus Epstein– using epithelial cells grown in monolayer tonsil keratinocytes in organotypic raft Barr Virus (EBV) is a common infection cell culture only supported a latent EBV culture. KSHV is a significant pathogen that establishes lifelong latency in B infection. Breakthrough came when in the immunocompromised, especially lymphocytes. EBV infection in the young primary oral keratinocytes grown as 3D those infected with HIV, and infection is is often asymptomatic but if infection rafts were efficiently infected with EBV associated with Kaposi sarcoma and is delayed until adolescence, can often and the virus underwent a full productive several other malignancies. Infected manifest as infectious mononucleosis or cycle. This EBV infection model showed saliva was known to be the route of glandular fever. Establishment of lifelong that the infection of epithelial cells led to transmission but the source of the virus latency may lead to EBV-associated the efficient production of new progeny in the saliva was unclear. In the rafts, lymphoid and epithelial cancers. The route and this tropism was an integral part of the KSHV lytic cycle was only initiated of infection of B cells was thought to occur EBV spread in the oropharynx. Likewise, a upon differentiation of the latently by oral transmission via epithelial cells better understanding of the transmission infected tonsil cells and newly assembled in the oropharynx, but evidence that EBV of another herpesvirus, Kaposi sarcoma- infectious particles accumulated in the could undergo productive replication in associated herpes virus (KSHV), was mature epithelial regions; thus infected epithelia was slight and infection studies gained from growing virus-infected tonsils could shed new progeny into saliva.

Stratum corneum Granular layer HPV late protein (green)

Spinous layer HPV early protein Basal layer (red)

Collagen + fibroblasts

Fig. 3. Recapitulation of HPV life cycle in organotypic raft culture. S. Roberts, University of Birmingham

68 Microbiology Today May 19 | microbiologysociety.org The intimate relationship between Future directions testing novel therapeutic compounds. human papillomaviruses and The continuing development of Advancement in understanding viral epithelial differentiation organotypic raft cultures to enable pathogenesis will come from the The use of epithelium equivalents high-throughput screening modalities incorporation of increasingly complex has been a revolutionary advancement will enhance the 3D epithelial models cellular components, e.g. immune cells, in the study of HPV biology. HPV of virus infection and replication as into the 3D models to more accurately replication is restricted to keratinocytes platforms for screening antivirals and mimic the site of virus replication. and the production of infectious particles is exquisitely dependent Sally Roberts Institute of Cancer and Genomic Sciences, College upon their differentiation. Infection of Medical and Dental Sciences, University of with the majority of HPV types (there Birmingham, Vincent Drive, Birmingham B15 2TT, UK are lots of them) results in benign warty lesions that are subsequently e [email protected] cleared by immune activation. But Sally Roberts has built a research portfolio studying a small number of HPV types that the molecular biology of human papillomaviruses and infect the squamous epithelia of Roberts Sally a centrepiece of her research is the use of physiological genital and oropharyngeal tracts are 3D epithelial models of the virus life cycle and virus-driven carcinogenesis. Sally is the cause of the majority of cervical an associate editor of Virology Journal, and was a past member of the Microbiology cancers along with a substantial Society’s Virology Division. proportion of other anogenital and oropharyngeal cancers. The virus infects Joanna Parish basal keratinocytes and proceeds to Institute of Cancer and Genomic Sciences, College manipulate the keratinocyte as it moves of Medical and Dental Sciences, University of up through the layers creating an Birmingham, Vincent Drive, Birmingham B15 2TT, UK environment conducive to the productive e [email protected] cycle of the virus. Joanna Parish has studied the molecular biology of The virus is dependent on the HPV for over 20 years and has unravelled mechanisms host cell to replicate and pushes the Joanna Parish of HPV genome replication, persistence and epigenetic otherwise postmitotic differentiating control of virus transcription utilising 3D epithelial models of HPV infection. Joanna keratinocytes back into cell cycle is an Editor of the Microbiology Society publication Journal of General Virology, and acquiring access to the cellular DNA was a past member of the Microbiology Society’s Virology Division. synthesis machinery. Once the viral genome has been amplified, the Why does microbiology matter? delay in differentiation is lifted and Sally: Over 15% of human cancers are known to have an infectious aetiology the final stages of capsid production and there still may be more associations to discover. Studying these infectious and virus assembly take place in the agents not only helps us understand oncogenesis and aids the design of effective mature regions of the epithelium. This vaccine strategies, but also enlightens our knowledge of the basic molecular and productive cycle can be recapitulated cell biology of our cells. fully in keratinocytes isolated from What is the most rewarding part of your job? anogenital and oropharyngeal tissues Joanna: I have the privilege of working with some of the best academic minds that harbour the circular HPV genome to answer our own important questions about how viruses manipulate cells to and grown in organotypic raft culture cause cancer. My scientific networks are built from those working within my (Fig. 3). Significant insights into the research group (undergraduates, graduates, postdoctoral scientists) to my local, molecular biology of the HPV life cycle national and international collaborations. I find this ‘team science’ approach and pathogenesis have come from the rewarding on many levels. use of the 3D culture system.

Microbiology Today May 19 | microbiologysociety.org 69 Human noroviruses and gut bacteria: friends, frenemies or both?

Coloured transmission electron micrograph of a section through several Norwalk virus particles. Matthew D. Moore Biomedical Imaging Unit, Southampton General Hospital/Science Photo Library One does not normally use phrases like ‘projectile Human noroviruses: not just cruise ships vomiting’ or ‘explosive diarrhoea’ casually, but in the case Human noroviruses are the leading cause of foodborne illness globally, of human noroviruses, these terms can often be applied. even though foodborne transmission of Norovirus gastroenteritis commonly manifests in the form noroviruses comprises around 20–30% of all cases. This is no surprise given of vomiting, diarrhoea and abdominal cramping – many a number of properties of human noroviruses that makes their control times in concert to a degree that would not be forgotten extremely difficult. These viruses are anytime soon. not effectively inactivated by many commercial disinfectants; can survive on surfaces for well over a month; onversely, a small portion of have a very low infectious dose; rapidly people shedding norovirus, evolve to escape host herd immunity; Canywhere from 5-30%, do not and are asymptomatically and post- display any symptoms despite shedding symptomatically shed. Although probably virus at nearly the same levels for the most well-known for incapacitating same duration. Like many questions cruise ships, many norovirus outbreaks surrounding human noroviruses, the happen in other settings such as schools, specific mechanisms for this are not well restaurants and long-term care wards. understood. Despite being generally self- Noroviral illness is so common that limiting, human noroviruses are still the (using rough, back-of-the-envelope fourth leading cause of foodborne death assumptions) in the US one could fill a and exact a major public health burden little over an Olympic-sized swimming on an annual basis. pool of foodborne norovirus diarrhoea

70 Microbiology Today May 19 | microbiologysociety.org monthly. That would be nearly 100,000 noroviruses in vitro had generally cell, the virions just bound the outside 32 oz (0.95 l) soda cups per day, in case been unsuccessful. The only way to of neighbouring cells without uncoating. you were wondering. cultivate human strains of the virus In terms of binding, epidemiological and was by feeding it to humans (which feeding studies showed that in some Trick or treat…or diarrhoea? can still be done today if a study is being cases infection was related to host blood The history of human noroviruses as conducted and you are desperate for type. Specifically, the majority of human we know them can be traced back to a some cash). This forced researchers norovirus strains were shown to bind gastroenteritis outbreak that occurred in the field to rely on related surrogate ‘histo-blood group antigens (HBGAs)’, in an elementary school in Norwalk, viruses, including a norovirus that infects which are carbohydrates related to blood Ohio during Halloween in 1968. The mice. Specifically, the major hurdle in type that are expressed in a number agent responsible for the outbreak was human norovirus cultivation appeared of tissues in the body, including the not known until 1972, when Dr Albert to be the uncoating stage of infection. intestinal tract. These HBGAs were at Kapikian and colleagues reported and This is because human norovirus least in part suspected of being a co- visualised noroviruses using immune genomic RNA could be transfected factor in norovirus infection, but what electron microscopy. Since that time, into cells and go through one stage of else was required for in vitro cultivation efforts to cultivate human strains of replication; however, upon lysing the was unclear.

Coloured transmission electron micrograph of a section through several Norwalk virus particles. Biomedical Imaging Unit, Southampton General Hospital/Science Photo Library

Microbiology Today May 19 | microbiologysociety.org 71 Score one for yogurt? A major breakthrough came in 2014. Dr Stephanie Karst, Dr Christiane Wobus, Dr Melissa Jones, Dr Jan Vinje and colleagues released a study demonstrating replication of human noroviruses in a human B cell line when enteric bacteria were included as a co-factor. Prior to this, enteric bacteria had been demonstrated to have HBGA-like carbohydrates on their surface, and one had recently had been shown to bind human noroviruses (Enterobacter cloacae). The report by Karst and colleagues suggested that enteric bacteria or their HBGA-like carbohydrates promoted norovirus replication in these B cells, in part by aiding viral adhesion to cells. The group was able to demonstrate that inclusion of residual enteric bacteria in norovirus-containing stool or specific doses of heat-killed Enterobacter cloacae facilitated replication. Further, the group reported that these enteric bacteria might aid in viral translocation across the epithelial cell layer to get to B cells underneath. Despite this breakthrough, the specific identity of the bacterial proteins or lipids associated with the HBGA-like carbohydrates and the Coloured scanning electron micrograph of Enterobacter cloacae bacteria. Juergen Berger/Science Photo Library specific effect of norovirus binding on bacteria is still not fully elucidated. A may inhibit and inactivate noroviruses. them from binding and infecting the number of studies surveying a broad For instance, Dr Changsun Choi and host cell. Although reports suggesting array of enteric and lactic acid bacteria colleagues observed reduction of two antiviral effects of certain bacteria on have demonstrated that numerous human norovirus surrogates during a noroviruses are sparse, the issue likely norovirus strains bind a number of lactic acid bacterial fermentation, and deserves further investigation. bacteria to different degrees. Overall, this others have demonstrated antiviral model has assisted and enabled study of activity of lactic acid bacteria against Enteric Mini-Mes human noroviruses, though with some other enteric viruses (like rotavirus) Another major breakthrough in the difficulty in replication. For instance, the whose replication has been reported to study of human noroviruses came in use of bacteria has allowed for the study be enhanced by enteric bacteria. Others 2016. Dr Mary Estes, Dr Robert Atmar of potential antiviral therapeutics for have suggested that certain bacteria and colleagues reported successful human norovirus. may reduce viral replication by binding replication of human norovirus in stem Further complicating these findings and sequestering potential infectious cell-derived human intestinal enteroids. have been reports that other bacteria norovirus particles, thus preventing These enteroids are basically made by

72 Microbiology Today May 19 | microbiologysociety.org

with“ numerous areas ripe for Ettayebi K, Crawford SE, Murakami K, investigation. Is infection only occurring Broughman JR, Karandikar U et al. in the epithelial layer or could it Replication of human noroviruses in stem Although reports also be occurring in B cells? What cell–derived human enteroids. Science specific bacterial proteins or lipids 2016;353:1387–1393. suggesting antiviral are responsible for binding to human Jones MK, Watanabe M, Zhu S, norovirus? Is there another mechanism Graves CL, Keyes LR, et al. Enteric bacteria effects of certain bacteria through which these bacteria aid promote human and mouse norovirus infection beyond aiding attachment or infection of B cells. Science 2014;346: on noroviruses are sparse, aggregation? Are there certain bacteria 755–759. that may act to inhibit human norovirus Moore MD, Goulter RM, Jaykus LA. Human the issue likely deserves infection? What host factors affect this Norovirus as a Foodborne Pathogen: transkingdom interaction? If there is one Challenges and Developments. Annu Rev Food further investigation. definitive conclusion that can be drawn Sci Technol 2015;6:411–433. from these exciting developments, it is Moore M, Jaykus LA. Virus–Bacteria that more research is needed. Interactions: Implications and Potential for the Applied and Agricultural Sciences. Viruses collecting stem cells from a host’s small Further reading 2018;10:61. “intestine and providing the necessary Almand EA, Moore MD, and Jaykus LA. Sullender ME, Baldridge MT. Norovirus growth factors to grow a ‘mini-gut’ Virus–bacteria interactions: an emerging topic interactions with the commensal microbiota. with a large number of differentiated in human infection. Viruses 2018;9:58–68. PLOS Pathog 2018;14:e1007183. intestinal epithelial cells. One major finding from this model was that enteric Matthew D. Moore bacteria were not necessary for human Department of Food Science, University of norovirus replication for a number Massachusetts, Amherst, USA of different human norovirus strains. e [email protected] Evidence from the study did suggest Matthew Moore graduated with BSc in Food Science that bile acids enhance infection and from Cornell University in 2010 and received his may be a necessary co-factor for some Matthew D. Moore D. Matthew PhD in 2016 in Food Science under the supervision human norovirus strains, as well as of Dr Lee-Ann Jaykus at North Carolina State University. After serving as a HBGAs. Further, the study suggested that postdoctoral fellow under the supervision of Dr Jason Folster at the US Centers it was epithelial cells that were being for Disease Control and Prevention from 2017–2018, Matt then joined the infected and not B cells. Replication was Department of Food Science at the University of Massachusetts, Amherst as an observed in these epithelial cells taken Assistant Professor. from all three major portions of the small intestine, suggesting that there was no specific localisation of replication What is the best career decision you have ever made? in the small intestine. However, the That is really difficult to answer! I feel like I have been unbelievably lucky to end possibility that bacteria may cause up with amazing mentors and peers throughout my career. Deciding to go into localisation of norovirus replication and/ food science and microbiology would be the best, as both communities are full of or enhance infection still remains a incredible people – I feel lucky to be a part of these scientific communities! possibility. What is the most enjoyable part of your job? More funding please! So many things are enjoyable. I would have to say the daily interaction with the fantastic people in our field as well as getting to work on such interesting topics. All of these interesting developments Also poop jokes. leave more questions than answers,

Microbiology Today May 19 | microbiologysociety.org 73 Humans coexist with more The than 100 trillion micro- organisms, including bacteria, fungi, archaea, intestinal viruses and protozoa that reside in multiple sites of microbiota the body, including the skin, lungs and reproductive in health tract. Those with the highest density and diversity are found in the gastrointestinal and (GI) tract (the intestinal microbiota) and make up the disease microbiome.

Katharine Seton and Simon R. Carding

he collective genome of all the pioneers. Depending on mode of introduction of solid food, the intestinal micro-organisms that reside in delivery, the infant’s initial intestinal microbiome starts to resemble that of Tand on the human body encodes microbiota will either resemble their an adult, becoming enriched in genes approximately 3.3 million genes, which mother’s vaginal microbiota, rich in associated with vitamin biosynthesis and is 100-fold greater than the human Lactobacillus, or their mothers skin polysaccharide degradation. genome. Whereas approximately 99.9% microbiota, rich in Streptococcus. Post- of genes within the human genomes of partum, the intestinal microbiota of How do we study the microbiome? two unrelated humans are identical, only the infant rapidly changes, increasing The intestinal microbiome makes an 10–20% of genes within the microbiome in diversity during the first two years, important contribution to maintaining are shared by two unrelated humans. in association with infant feeding. human health, with alterations in its This emphasises the importance of Breast milk, which harbours hundreds make-up and/or function (microbial the microbiome in defining humans as of species of bacteria, provides dysbiosis) being associated with individuals. infants with a source of beneficial and numerous diseases. However, to health promoting (probiotic) bacteria identify dysbiosis we first need to How do we acquire our microbiome? including Bifidobacteria and Lactobacilli. define a healthy intestinal microbiome. Microbial colonisation begins during By contrast, formula-fed infants The development of DNA sequencing and soon after birth, with the mother have a distinct intestinal microbiota, technologies has significantly advanced being the principal source of microbial with fewer probiotic bacteria. Upon and accelerated our understanding

74 Microbiology Today May 19 | microbiologysociety.org of the intestinal (faecal) microbiota and, in particular, bacterial taxonomy using 16S rRNA based sequencing and the functional capability of the microbiota using whole-genome shotgun sequencing. These culture- independent sequencing methods achieve proportionate analysis of microbial abundances within a complex community of microbes, and the identification of ratios of bacterial families and genera. However, care must be taken when collecting, transporting, storing and processing (faecal) samples to preserve baseline microbial abundances. Some investigators have argued that this analysis should be combined with quantitative microbiome profiling, as microbial load can vary substantially between different samples from the same individual, and between individuals.

What influences the composition of a healthy microbiome? Difficulties in defining a healthy Scanning electron micrograph of Bifidobacterium bacteria. Magnification: x3,000 when shortest axis printed at intestinal microbiome extend beyond 25 mm. Dennis Kunkel Microscopy/Science Photo Library limitations of experimental techniques. Both the composition and the temporal proton pump inhibitors have a strong in which microbes process dietary stability of the intestinal microbiome are effect on the gut microbiome, as do fibre and resistant starch to generate personalised and individual. Performing antibiotics, metformin, statins and short-chain fatty acids (SCFAs). longitudinal studies on large cohorts, laxatives. Antibiotic-associated changes SCFAs are an important source of combined with data compilation of in the microbiome can extend well energy for intestinal epithelial cells environmental, behavioural, genetic and beyond course completion. Of note, and they promote local hormone and anthropometric measures, enables the these covariates together explain less neurotransmitter production which dynamics of the microbiota and major than 20% of variation seen in healthy influences GI motility and appetite covariates of microbiome composition individuals’ microbial compositions. control. The microbiome also provides its to be identified. Several large-scale host with a source of essential vitamins microbiome projects, including the How does the intestinal and minerals, such as folates, vitamins Human Microbiome Project, the Flemish microbiome promote health? K, B2 and B12, and biotin. Gut Flora Project, the Dutch LLDeep, and The major contribution of the intestinal The microbiome promotes the the American Gut Project, have identified microbiota to maintaining human development of both the immune and major covariates that include age, health is digestion and the processing enteric nervous systems. Mice deficient gender, stool frequency and consistency, of food and complex plant-based in key microbial recognition receptors drug intake and dietary factors such polysaccharides (fibre). The colon can be (i.e. toll-like receptors; TLRs) have as sugar intake. Among medications, considered a large fermentation vessel reduced numbers of enteric neurons and

Microbiology Today May 19 | microbiologysociety.org 75 experience defective intestinal motility. sensorimotor connections, influencing and the brain. However, the majority of Sterile, germ-free mice are severely the enteric neuroendocrine system by human microbiome–disease studies immunocompromised with defective immune activation. Different bacteria carried out to date are observational and development of gut-associated lymphoid within the microbiome are a source associative providing limited insight into tissues and antibody production, in of immunomodulators and regulators functional causation: cause vs effect of addition to neurological and central of endocrine hormone action and can intestinal dysbiosis and disease aetiology nervous system (CNS) deficits. Microbial catabolise diet-derived amino acids to is poorly understood. Animal studies colonisation in early life promotes the synthesise various neurotransmitters can be utilised to explore intestinal development of the innate immune including GABA, serotonin, histamine dysbiosis and disease pathogenesis. For system and immune tolerance and and L-DOPA. Therefore, the microbiome example, transplanting human faeces contributes to host defence against can have an impact on motor control, from obese patients into germ-free pathogen infection through competitive learning, memory and emotion mice resulted in them becoming obese. exclusion and the production of (primarily stress and depression). If However, differences in GI anatomy and antimicrobial proteins. microbiome alterations result in a loss physiology and in the microbiota of mice In addition to its local effects of homeostasis of these systems, then versus humans, in addition to obvious on intestinal health, the intestinal diseases affecting mental health could differences in lifestyle and behaviour, microbiome has an impact on other ensue. make it difficult to translate findings organ systems, including the brain, via from animal studies directly to humans. the bidirectional gut–brain axis, which How does the microbiome Relating functionality of bacterial involves neural pathways as well as influence disease? genus/species to the abundance immune and endocrine mechanisms. Intestinal microbial dysbiosis and alteration in disease states is another The intestinal microbiome can exploit reduced diversity of bacterial, and way of exploring intestinal dysbiosis this axis to influence signalling increasingly viral, populations is on disease progression. For example, within the CNS and modulates host associated with disorders affecting the Faecalibacterium prausnitzii is a resident behaviour via modification of autonomic GI-tract, liver, vasculature, lungs, joints intestinal bacterium that possesses anti-inflammatory properties and is less abundant in patients with inflammatory bowel disease (IBD).

How do we treat microbial dysbiosis to restore health? Targeting the intestinal microbiome as a therapeutic intervention strategy may be of benefit in diseases associated with intestinal microbial dysbiosis. Three approaches can be considered. First, administration of probiotic micro- organisms. Second, the consumption of prebiotics such as fructans, inulin, fructo-oligosaccharides, galacto- oligosaccharides and lactulose that support the growth of beneficial microbes. Third, wholesale microbiota replacement by faecal microbiota Coloured transmission electron micrograph of Clostridium difficiledrug-resistant bacteria. transplantation (FMT). FMT has proven Biomedical Imaging Unit, Southampton General Hospital/Science Photo Library to be a very effective treatment and

76 Microbiology Today May 19 | microbiologysociety.org cure for recalcitrant Clostridium difficile infection (rCDI) and is becoming an Katharine Seton established treatment option within the Gut Microbes and Health Research Programme, NHS for rCDI. Beyond its use in treating Quadram Institute Bioscience, Norwich Research chronic GI infections, several FMT Park, Norwich, Norfolk NR4 7UA, UK clinical trials are underway exploring its Katharine Seton attained her bachelor’s degree in potential use in other disease including Biomedical Sciences at Newcastle University in 2016. IBD, irritable bowel syndrome and She then moved to Norfolk to undertake a PhD. Her myalgic encephalomyelitis. Seton Katharine research aims to determine whether there is an In summary, humans have evolved abnormal immune response to the microbiota in myalgic encephalomyelitis/ with their microbiome, establishing chronic fatigue syndrome (ME/CFS) patients. a mutualistic relationship in which the microbiome, in return for being Simon Carding provided a ‘home’, plays a central role Norwich Medical School, Faculty of Medicine and in maintaining life-long health. Further Health Sciences University of East Anglia, Norwich research is now needed to define the NR4 7TJ, UK nature and molecular basis of microbe– Quadram Institute Bioscience, Norwich Research host interactions in the GI-tract and Park, Norwich, Norfolk NR4 7UA, UK elsewhere, using complimentary culture- e [email protected] dependent and -independent approaches Simon Carding Simon Carding is Professor of Mucosal Immunology and technologies. Appropriate in vivo pre- at the University of East Anglia and leader of the Gut Biology Research clinical studies with subsequent human Programme at the the Quadram Institute. His research focuses on understanding studies and clinical trials can then lead how gut microbes communicate with their host and the role that this cross-talk to the development of evidence-based plays in establishing and maintaining health, and in diseases affecting the gut interventions that target the microbiome and other parts of the body, including the brain. to promote, maintain or restore health. What do you see as your greatest achievement to date? Further reading Carding S, Verbeke K, Vipond DT, Corfe BM, Katharine: Looking back, I believe my greatest achievement to date is having Owen LJ. Dysbiosis of the gut microbiota in been driven and focused enough to complete an undergraduate degree, then disease. Micro Ecol Health Dis 2015;26:26191. undertaking a PhD, despite having myalgic encephalomyelitis/chronic fatigue Falony G, Joossens M, Vieira-Silva S, Wang J, syndrome (ME/CFS). In high school, I completed my GCSEs while attending Darzi Y, et al. Population-level analysis of gut school part-time and pursuing a career in academia seemed unattainable. It feels microbiome variation. Science 2016;352:560. like a huge achievement to have gotten this far in my research career. Obata Y, Pachnis V. The Effect of Microbiota Simon: Having the opportunity to work with and mentor some very talented and the Immune System on the Development scientists and seeing them go on to establish successful careers both within and and Organization of the Enteric Nervous outside of science. System. Gastroenterology 2016;151:836. What is the most rewarding part of your job? Powell N, Walker MM, Talley NJ. The mucosal Katharine: As part of my PhD ‘Defining autoimmune aspects of Myalgic immune system: master regulator of Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)’, I am undertaking bidirectional gut-brain communications. Nat a human study which involves collecting samples from severe, housebound Rev Gastroenterol Hepatol 2017;14:143. patients. Interaction with these patients is the most rewarding part of my job, as Scott KP, Antoine JM, Midtvedt T, van Hemert it enables me to appreciate first-hand the impact my research could have. S. Manipulating the gut microbiota to maintain Simon: Working in an exciting and dynamic area of biomedical research that is health and treat disease. Micro Ecol Health Dis never boring and is both challenging and rewarding. 2015;26:25877.

Microbiology Today May 19 | microbiologysociety.org 77 Annual Conference 2019 #Microbio19 8–11 April, ICC Belfast, UK In April the Microbiology Society welcomed over 1,300 delegates to its flagship Annual Conference, which took place in Northern Ireland for the first time in the Society’s history. The line-up of expert speakers from across the globe presented over four days on a wide range of topics. The event included: • 29 scientific sessions • Talks from 130+ invited speakers • Over 290 offered talks • Over 600 posters • Five sessions dedicated to professional development: ° CV workshop ° Managing a research laboratory ° Peer review ° Research and publishing ethics ° Resilience in careers • Two Hot Topics: ° Creating a path – how single cells can solve mazes, see round corners, and find out where they ought to go by Professor Robert Insall, Cancer Research Institute, UK. ° Paralytic disease caused by enteroviruses: the role of non-polio serotypes by Javier Martin, National Institute for Biological Standards and Control (NIBSC), UK. • Four Poster Prizes: Microbiology Society Journals’ ‘Most Promising Science’ Prize, Early Career Microbiologists’ Forum Poster Prize, Peoples’ Choice Poster Prize , and the Howard Dalton Young Microbiologist of the Year Prize. If you presented work at our Annual Conference 2019, why not submit your article to one of our journals to continue to support the work of the Microbiology Society and the microbiological community? Visit the Microbiology Society journals platform to find out more microbiologyresearch.org( ). Watch some of the videos from year’s Annual Conference on the Microbiology Society YouTube Channel (microbiologysociety.org/YouTube). All photos: Ian Atherton photos: All

78 Microbiology Today May 19 | microbiologysociety.org Keep up-to-date with events, follow the Society on Twitter:

@MicrobioSoc rabbit75_ist/Thinkstock Annual Conference 2020 #Microbio20

• Exploring the eukaryotic tree of life 30 March–3 April, EICC Edinburgh, UK • Genes on the move Preparation is now well underway for our Annual Conference 2020 at the • Marine microbiology Edinburgh International Conference Centre (EICC). The event will take place for • Novel eukaryotic drug targets an extended five days as part of our 75th anniversary celebrations. • Outer layers of microbiology • Phage biology On the first day of Annual Conference to stay. To support you with this, our • Public health microbiology 2020, the Microbiology Society will booking agent Reservation Highway • Skin-full of viruses be hosting a special day-long series (reservation-highway.co.uk/micro20) • Toxins and antitoxins of Fleming Lectures organised by has secured a range of accommodation • Veterinary microbiology an appointed committee of previous options to suit all budgets throughout • Virus modulation of cell stress Fleming Prize winners, chaired by Nobel Edinburgh, at discounted rates. Prize winner Sir Paul Nurse. The day is Forums designed to provide value to everyone in Programme • Environmental and applied the microbiology community, including As always, Annual Conference microbiology forum early career scientists. You will be is designed to cover the breadth • Genetics and genomics forum able to attend this day for free when of microbiology research and its • Microbial infection forum registering for Annual Conference 2020. comprehensive scientific programme • Microbial physiology, metabolism Abstracts will open in August 2019 has over 30 sessions taking place in a and molecular forum for the Annual Conference sessions range of formats: Virology Workshops running from the Tuesday until the • Cell stress and viruses Friday, and the submissions deadline will Fleming talks • Clinical virology be Monday 9 December 2019. • Genetic control of mosquitoes • DNA viruses • Orchestrating gene regulation across • Negative-strand viruses the genome and across the cell Destination Edinburgh • Positive-strand and double-strand Edinburgh is a diverse and vibrant city, • Palaeomicrobiology: what ancient RNA viruses steeped in history. The backdrop of DNA can tell us about pathogens • Retroviruses Arthur’s Seat, the Pentland Hills and from the past Edinburgh’s waterfront make the city an • Predatory Bdellovibrio bacteria – Professional Development Sessions exciting event destination. If you extend 58 years of understanding them as • Bioinformatics your stay after Conference, there are allies against AMR infections • Entrepreneurship plenty of attractions to visit, such as • The expanding virosphere • Fellowship Edinburgh Castle, the National Museum • Visualising bacterial nanomachines • Teaching Microbiology in Higher of Scotland, the Scottish Parliament in situ by electron cryotomography Education Symposium and the Royal Yacht Britannia. Visit • Unconscious bias edinburgh.org for further information. Main Symposia Sign up to our newsletter and • AMR follow the Society on social media Accommodation • Back to the future to receive regular updates about Edinburgh is a popular destination and • Bacteroidetes events and Society news, or visit we therefore highly recommend you • Bioproduction and biomaterials microbiologysociety.org/events secure your accommodation as soon • Dynamic cell for information. as possible to ensure you have a place • Epigenetics

Microbiology Today May 19 | microbiologysociety.org 79 Focused Meetings Keep up-to-date with events, follow the Society Juneand Events 2019 update on Twitter: @MicrobioSoc

The first two Focused Meetings of this year’s series will take place in June, but there is still time to book your place to attend. Both events will feature a programme of renowned speakers and showcase new and emerging research, while also offering valuable networking opportunities. Microbiology Society members can register at discounted rates and members also have access to Microbiology Society grant opportunities.

Anaerobe 2019: Changing perceptions of anaerobic bacteria; #Anaerobe19 from pathogen to the normal microbiota and back 13–14 June 2019 | Jurys Inn Hotel, Cardiff, UK microbiologysociety.org/Anaerobe19 Anaerobe 2019 is being held in Cardiff, where the UK Anaerobe Reference Unit is based, in association with the Society for Anaerobic Microbiology and the Welsh Microbiology Association. The meeting will provide insights into the current and future impact of anaerobic bacteria in human health and disease, addressing the implications of recent microbiota studies, as well as the continued threat of emerging and re-emerging anaerobic infection. Anaerobic clinical microbiology remains a challenge due to specialist culture requirements, coupled with the increase in and spread of antimicrobial resistance. The normal human microbiota is primarily composed of anaerobic bacteria and has been recognised as a source of life-threatening anaerobic infection since the early days of microbiology in the late 1800s. More recent metataxonomic and metagenomic sequencing has extended interest in the potential role of the microbiota in a plethora of other aspects of human health, from obesity to mental health. In addition, the

successful use of faecal microbiota transplants for the treatment D ennis rary Kunkel Microscopy/Science Photo Lib of clostridial infection raises potential unchartered long-term consequences and possibilities. Follow us on Twitter @MicrobioSoc using the hashtag #Anaerobe19.

British Yeast Group: Discovery to Impact #BYG19 26–28 June 2019 | County Hotel, Newcastle, UK microbiologysociety.org/BYG19 The British Yeast Group (BYG) Focused Meeting is the second event in the Society’s 2019 programme and takes place in Newcastle. Yeasts have been used extensively for over a century to explore fundamental aspects of living systems, and this meeting will focus on the theme of ‘Discovery to Impact’. The programme will feature a range of keynote talks from invited speakers and will give early career yeast researchers the opportunity to present their recent research results through a series of posters and offered oral presentations covering the following topics: fundamental cellular processes, including metabolic cycles, chromatin biology, regulation of gene expression and control of quiescence; yeasts as disease models; pathogenic yeasts and biotechnological applications of yeasts.

80 Microbiology Today May 19 | microbiologysociety.org Microbiology Today May 19 | microbiologysociety.org 81 Spotlight on Grants:

Colonising the causes

of gastric cancer Helen with Dr Rossiter in the lab. Helen Jordan Harry Smith Vacation Studentships facilitate short research Dr Rossiter described Helen as “a great addition to the lab over the

projects for second year undergraduates during their summer summer months. She was able to vacation. By funding such opportunities, the Microbiology Society master a range of culture techniques, invests in the professional development of budding research independently plan experiments and interpret her results. Her work, and the scientists and provides opportunities for early career researchers work of others in my lab, will further our to gain supervision experience. understanding of complex polymicrobial interactions and their role in gastric

carcinogenesis.”“ ast summer, BSc Biomedical Helen said, “In terms of my academic Helen said: “The highlight of the Sciences student Helen Jordan career, it has cemented for me a drive project for me was seeing my name and was awarded a studentship by and desire to pursue a PhD. The project L data I had produced on a poster Amanda the Society, where she worked under gave me my first experience of research presented at a H. pylori conference the supervision of Dr Amanda Rossiter and all that comes with working in a lab. in Helsingor, Denmark. The skills I at the Institute of Microbiology and I feel very prepared for my third year have learnt this summer are proving Infection, University of Birmingham, UK. dissertation and my PhD applications invaluable. I would like to thank the Helen investigated interactions between with this project under my belt.” Microbiology Society once again for Helicobacter pylori and the human their support.” gastric microbiome, and how changes Applications for the Harry Smith in frequency of such microbes can be Vacation Studentship open in December correlated with the development of Deciding to undertake a lab each year. To find out more, visit our gastric cancer. website (microbiologysociety.org/ During her studentship, Helen project was once of my best harrysmithvacationstudentships). mimicked the conditions of the gastric microbiome environment in vitro, so decisions at university so far. To find out more about the wide range that she could observe the growth of of grants to support Microbiology Society H. pylori, before co-culturing with members, visit the grants area of our samples of Actinomyces oris and website (microbiologysociety.org/ Since Helen left the lab, Dr Rossiter Campylobacter jejuni. From this co- grants). culture, Helen identified that A. oris and her research group have been appeared to be responsible for growth exploring in depth the mechanisms Kirti Mistry inhibition of H. pylori in the gastric by which cancerous gastric microbes Grants and Professional Development microbiome. The data gathered by Helen influence the growth of H. pylori, and how Officer will contribute to a manuscript that is such behaviour modulates epithelial cell [email protected] currently in preparation. “responses in an ex vivo organoid model.

82 Microbiology Today May 19 | microbiologysociety.org Careers Focus: Putting together your CV

During the Annual Conference remember to only include brief how the applicant is right for the job, 2019, we hosted a CV workshop details of research degrees, as long it’s unlikely a recruiter will spend time as it’s appropriate to the potential on it. Make sure to use the cover letter in collaboration with Miriam employer. too; although some online application Windsor, Pirbright Institute, UK. • Employment – again, most recent portals make these optional, we suggest During the session we covered first. You may wish to itemise you always use this opportunity to shine the purpose of CVs (also known relevant achievements, skills and and tell them just how you fit the person as résumés), cover letters which responsibilities for each role you’ve specification. had. Like any piece you’ve written, your almost always accompany them • Competencies – what are you good CV should have a clear objective. In this and what to include to help you at? What can you bring to the role? case, to communicate to an employer get the job. Some of the points This includes transferrable skills just how great you’ll be at the job. Make that came up during the session such as project management, sure you think about your language analysing data and written and oral and audience. CVs and covering letters are in this article. communication skills. take a lot of careful time and attention, • Training and professional and lots of reviewing is required too to or a non-academic CV, there is development – have you had any make sure you are making your point no perfect, one-size-fits-all CV – training that is relevant to the role accurately. Don’t forget to keep it up to Fthere are many ways to structure you’re applying for? date so that you don’t have to start from them and you will find that people will • References – don’t forget to check the beginning again next time! give you slightly different advice. As a before including up to two people as We have focused on chronological scientist, you should work on conveying referees. CVs here. For more information on the transferrable skills you have gained • Other things to make sure you specific items to include in academic while conducting your research. include are details to set you CVs, please see the Vitae website Some common components of a apart. This can include positions of (vitae.ac.uk). standard, chronological CV are: responsibility, for example where • Personal details – to tell readers who you’ve taken up extra activities that you are and how to contact you. You lead to the development of leadership should title your CV with your name skills. It’s customary to also include (not ‘Curriculum Vitae’!) and you a section on your interests, but try to could include your LinkedIn URL here keep this too, as long as it’s kept up to date. relevant to the job. Many people It’s not customary to include a photo include a personal statement on their or information about gender, age or CV – but keep this brief if you do. nationality on CVs in the UK. It is clear from the above that it’s • Education – with the most recent important to tailor your CV to the role for listed first. Don’t include every single which you’re applying. When confronted school qualification you’ve had and by a CV that makes no effort to showcase

Microbiology Today May 19 | microbiologysociety.org 83 Open research: it’s more than open access

In the last issue of Microbiology Today we wrote about open access (OA), copyright, and author rights. In this article we discuss the wider world of open research, also known as open science and open scholarship.

pen research has developed reproducibility by clearly identifying ‘Reusable’, the FAIR principles were over the last twenty years in the precise protocols used in a given launched in 2016 in response to this Oresponse to a combination of lab, and the results associated with that challenge. Many people assume FAIR factors, including the open access protocol. For individual researchers the applies only to data, but the same movement, funders’ need to map the increased visibility and engagement principles guide many other aspects of returns on their research investments, associated with open methods, data open research, such as open protocols concerns about research reproducibility and code can lead to new collaborations and methodologies, and open source and research waste, and a desire to and drive the creation of new research code. properly recognise researchers for all questions. Many organisations and Rich metadata describing their efforts rather than simply their funders are now giving researchers research outputs is key in making published output. It covers many aspects credit for their open research objects, them ‘findable’: including items such of research, from laboratory notebooks as well as journal articles. as keywords, author names, funding and data, to collaboration through data and an abstract will make sure scholarly social networks, to citizen FAIR principles for open research that search engines and other machines science. One of the biggest challenges in open will be able to find the research object. Much like open access, open research is good data management, ‘Accessibility’ relies on standard research carries with it benefits for which facilitates discovery and protocols for retrieving research objects the whole scholarly community. Open knowledge exchange for both humans – from a researcher’s perspective the methods and open data, in particular, and machines. Standing for ‘Findable’, key to accessibility is to use a compliant can reduce research waste and aid ‘Accessible’, ‘Interoperable’ and repository or platform, such as those described below. For research outputs Open to be ‘interoperable’ they need to use protocols community agreed standards and Citizen Open contain links to related information using science data persistent identifiers like digital object identifiers (DOIs), which allow machines to navigate easily between research objects. Open research Lastly, clear usage licences (such as the Open Open Creative Commons licence described in education source the February issue of Microbiology Today: microb.io/2GTfMtB) help researchers and machines understand the ways in which Open Open they can ‘reuse’ the research objects. collaboration evaluation Making your research open The Society’s journals work with Components of open research. several FAIR-compliant open research

84 Microbiology Today May 19 | microbiologysociety.org initiatives* and we encourage you to make use of them. They all offer Publishing for the community free services, and every research object in these initiatives has a DOI, so they microbiologyresearch.org are easily citable and are usually counted in research evaluation exercises. MICROBIOLOGY First up is protocols.io, a browser- mic.microbiologyresearch.org based tool for open methods which #MicrobioJ meets the FAIR principles. We all know that optimising protocols is time- consuming and that the information is often locked in lab notebooks. One of JOURNAL OF the things we love about protocols.io is GENERAL VIROLOGY that researchers can follow experiments jgv.microbiologyresearch.org step-by-step in real time and record #JGenVirol their changes, keeping an accurate record of their method and making it easy to write up for publication. JOURNAL OF We also work with data MEDICAL MICROBIOLOGY repositories such as figshare jmm.microbiologyresearch.org (figshare.com), Dryad (datadryad.org), #JMedMicro and Zenodo (zenodo.org), as well as Microreact for genomic epidemiology (microreact.org). These services allow researchers to upload large MICROBIAL GENOMICS data sets; being FAIR, these are vastly mgen.microbiologyresearch.org superior to the older ‘supplementary #MGen data files’ associated with journal articles. We recommend CodeOcean INTERNATIONAL JOURNAL OF (codeocean.com) for sharing code. SYSTEMATIC AND EVOLUTIONARY Unlike most other services, CodeOcean gives researchers the ability to execute MICROBIOLOGY ijs.microbiologyresearch.org published code without installing anything on their computers – you can #IJSEM even change parameters, modify the code and upload data to see how results change, without needing specialist ACCESS MICROBIOLOGY software. acmi.microbiologyresearch.org #AccessMicro

*We do not receive revenue from these initiatives and are promoting them only We hope that you’re finding these articles useful. If there is a topic you because our team truly believes they are would like us to address, email us at [email protected]. useful tools for our members.

Microbiology Today May 19 | microbiologysociety.org 85 The Global Sustainability Development Report on the Sustainable Development Goals The Global Sustainability Development Report To celebrate our 75th anniversary in 2020, we are The United Nations Sustainable embarking on a project that will demonstrate the value Development Goals (UN SDGs) are a call for action by all countries – low-, middle- and raise the profile of microbiology in addressing and high-income – to promote prosperity the UN Sustainable Development Goals. In this issue while protecting the planet. As we write this article, the world has less than 12 of Microbiology Today, we present a major scientific years remaining to achieve the ambitions initiative taking place at the international level: The Global of the 2030 Agenda for Sustainable Development. According to the latest Sustainability Development Report. report from the Intergovernmental Panel on Climate Change, we also have less than 12 years left to limit the global average temperature rise to 1.5 °C. In the next few months, the attention of the international scientific community will be focused on the Global Sustainability Development Report (GSDR), a document that aims to provide guidance from a scientific perspective to support policy- makers in striving towards achieving the SDGs.

The Independent Group of Scientists The next GSDR will be published this year and will be the first of a quadrennial series that will inform the high-level

United Nations global reviews of the 2030 Agenda at

86 Microbiology Today May 19 | microbiologysociety.org The Microbiology Society’s ‘A Sustainable Future’ project will promote knowledge exchange by bringing together microbiologists, scientists, industry, NGOs and policy-makers, to champion the importance of microbiology in sustainable development. Microbiological expertise will be used to explore solutions and influence national and international implementation plans. This will drive us towards the Society’s vision of a world in which the science of microbiology provides maximum benefit to society. Read our article published in the February issue on the SDGs project for more information (microb.io/2TmNlee). We spoke with Professor Otto Cars, founder of ReAct – Action on Antibiotic Resistance, about the UN’s role in devising sustainable and global solutions to tackle AMR. Professor Cars highlighted that the world has failed to keep pace with the issue of AMR, despite many proposals in recent decades. He further explained that, if AMR cannot be eliminated, it can still be managed through concerted efforts to slow down its pace. ReAct recently urged the international community to take up the work on AMR, highlighting that low-income countries experience the combination of the greatest burden of infectious diseases and the weakest healthcare and agriculture systems. It is hoped that the GSDR will acknowledge the need to increase financial and technical support from global funds to support countries in the early phases of implementing National Action Plans on AMR. the UN. The report is expected to make Ban Ki-moon appointed 15 experts, the limited resources allocated to the recommendations ‘on the state of representing a variety of backgrounds, GSDR process. global sustainable development from scientific disciplines and institutions, to a scientific perspective’ and provide draft the GSDR. Endah Murniningtyas The GSDR and microbiology the lessons learned during the first (Indonesia) and Peter Messerli The microbiology community is in a four years of implementation of the (Switzerland) serve as co-chairs of the unique position to help tackle many of SDGs, ‘while focusing on the challenges, Independent Group of Scientists (IGS) the SDG targets. Microbiologists have addressing new and emerging issues supported by a task team co-chaired by been working for decades on problems and highlighting emerging trends and six UN entities. The disciplines of biology like antimicrobial resistance (AMR), a actions that may have an overall effect and microbiology are represented phenomenon that remains a threat to on sustainable development’. Before by Katherine Richardson (Denmark), global development at large. Background leaving office, former Secretary-General Ernest Foli (Ghana) and Peter Messerli work on the GSDR highlights that more (Switzerland). Scientists from around research and development investments the world have recognised the IGS’s high are needed in the field of antimicrobial interdisciplinarity, but have also research and that SDGs should be noted that the group will used as a platform through which have to work within AMR’s threat to the world’s sustainable development can be addressed collaboratively.

Please visit microbiologysociety. org/SDGs for further details on the ‘A Sustainable Future’ project, including opportunities to contribute.

Microbiology Today May 19 | microbiologysociety.org 87 Championing Microbiology and the

Microbiology Society

Champions are members who volunteer in their local place of work or

study. They get involved in a wide variety of activities and initiatives to help raise awareness of microbiology and the Microbiology Society. Through their actions – and the actions of many others of you who aren’t specifically designated ‘Champions’ but who do similar things – the “ Society’s impact, influence and membership continues to increase.

Ed Cunningham-Oakes, a Society Champion, has said:

One of the greatest things about being a Society Champion is being at the frontline of networking and funding for researchers in the field, and being given the opportunity to disseminate useful information at a plethora of networking events. You can travel, meet other researchers, and become a hub of societal information and opportunities. I would highly recommend becoming a Champion to anyone looking to develop holistically, both as a researcher in the field, and an individual.

Have you ever the Society in your role. Find out more Whatever your involvement – as a formal about the Society Champions scheme and Champion or an informal one, you make “considered becoming a how you can get involved on our website a very significant difference and help Society Champion? (microbiologysociety.org/champions). bring microbiologists together. Do you not have a Champion based at If you don’t want to be a Champion If you have any questions or your institution or in your local area? in the formal sense, you could be one need any support please contact us at Being a Champion is a great way to simply by helping spread the word about [email protected] develop new skills, give something back, the Society to a friend or colleague. Word or call +44 (0)20 7685 2680. or you can use your involvement to help of mouth helps bring the Society to the advance your own career. As well as attention of friends, work colleagues and Paul Easton access to a budget to support Champion- students who may not yet be members, Head of Membership Services, led initiatives, you’ll also benefit from but could be, and helps to strengthen the [email protected] great support and encouragement from microbiology community and networks.

88 Microbiology Today May 19 | microbiologysociety.org Society Champions Find out who the Society Champions are in your institution or local area:

Northern Ireland Scotland England Chris Proctor Ulster University Connor Bamford University of Glasgow Eastern Daniel Storey Queens University Belfast Elizabeth Wignall-Fleming MRC-University Lisa Crossman University of East Anglia Georgiana Parau Queens University Belfast of Glasgow Centre for Virus Research Nicola Crewe University of Lincoln Linda Oyama Queen’s University Belfast Katherine Duncan University of Strathclyde London Lindsay Broadbent Queen’s University Belfast Kirsty Robb University of Strathclyde Arikana Massiah St Thomas’ Hospital, London Sara Pidcock Queens University Belfast Sara Clohisey The Roslin Institute Sreyashi Basu University College London Yinka Somorin Queens University Belfast Zoe Leckie University of Glasgow Midlands Alice Lanne University of Birmingham Anja Dokic University of Birmingham Republic of Ireland Carl Aston University of Nottingham Gerard Sheehan Maynooth University Colman O’Cathail University of Nottingham Nathaniel Cole Maynooth University Ethan Iles Chesterfield Royal Hospital Sinead Corr Trinity College Dublin Magdalena Karlikowska University of Warwick Nathan Ashley ALS Laboratories Wales Rebecca Philp Science Oxford Benjamin Johns University Hospital of Wales Ruth Nottingham University of Nottingham Daniel Morse Cardiff University Saba Amir Nottingham Trent University Ed Cunningham-Oakes Cardiff University Vicky Smith University of Nottingham Eleanor Furness University of Aberystwyth North West Lauren Kerr Cardiff Institute of Infection and Angharad Green University of Liverpool Immunity Chloe James University of Salford Michael Pascoe Cardiff University Kate Baker University of Liverpool Dzyuba /iStock Maria Afonso University of Liverpool South East Alicia Russell John Innes Centre, Norwich Overseas Chinyere Okoro University of Surrey Arindam Mitra Adamas University, India Laura Petch University of Kent Alya Redhwan Princess Nourah University, Saudi Arabia Louisa Wallace University of Surrey Ayman Ahmed Sudan Matthew Herdman University of Oxford Bauyrzhan Tashmukhambetov Kazakh National Medical University, Kazakhstan Michael Macey The Open University Gayetri Ramachandran Institute IMAGINE, France Robert Will University of Cambridge Ikbal Agah Ince Acıbadem University, Turkey South West Jinxin Zhao Monash University, Australia Nigel Brown retired, previously University of Manoj Pradhan Nepalese Army Institute of Health Sciences, Nepal Edinburgh Maria Davis University of Regina, Canada Ruth Maclaren Sciencedipity Marilia Costa Paraiba State University, Brazil Tina Joshi University of Plymouth Nilay Joshi Unique Pharmaceutical Laboratories, India Yorkshire Sagar Aryal St Xavier’s College, Nepal and Kathmandu Center for Genomics and Research Laboratory Alex Remmington University of Sheffield (KCGRL), Nepal Lee Sherry University of Leeds Omololu Fagunwa University of Huddersfield

Microbiology Today May 19 | microbiologysociety.org 89

Early Career Microbiologists’ Forum Update: Communications, conferences and careers

pril marked the third Annual Representative. It is an excellent Conference since the opportunity for anyone interested in Aformation of the Early Career science communication, developing their Microbiologists’ (ECM) Forum. Year writing skills or learning more about a real treat to see her demonstrate the on year, the contributions made by how the Society communicates with its activity at the Society Showcase last early career researchers to the event members and the public. In this role, I September – it is an inspired creation. become more evident. We saw ECMs sit on the Communications Committee Senga’s communication skills and the continuing to play an active role in all and help to highlight the viewpoint of story behind how she got involved in aspects of the week, from running the early career researchers. The position outreach will make for an excellent talk pre-conference networking event to also involves becoming a member of at the Summer Conference. co-chairing many of the sessions. There the Microbiology Today Editorial Board, The Summer Conference will host was also a noticeable increase in the allowing you to put forward your invited speakers who will present across number of offered oral slots across the suggestions for the quarterly themes a range of microbiology topics. There event, highlighting the effort made by and authors. It is a great insight into how will also be a careers session that the the Microbiology Society to provide a the Society runs its communications ECM Forum Conferences Representative platform for early career researchers to platforms. Alison MacFadyen believes will be highly present their work. The second opportunity that I beneficial to the attendees, due to the I wanted to use this update to wanted to highlight is the return of array of different backgrounds included. promote two fantastic opportunities the ECM Forum Summer Conference, The panel will include representatives that the Society offers early career scheduled for 20–21 June at Trinity from the Industrial Biotechnology microbiologists. The first is particularly College Dublin, Ireland. This is back for Innovation Centre (IBiolC), Pint of Science timely. Elections for positions on the ECM its second instalment after the inaugural and West Cork Distillers. If you are Forum Executive Committee open on 3 event in 2018 and promises to be even considering a career outside of academia June, so do keep an eye on the Society’s better this year. The Conferences and or just want to learn more about the jobs website and social media platforms if Division Representatives have worked available to early career microbiologists, you are interested in having your say in hard to implement the feedback given then this is not to be missed. how the views of ECMs are represented. by the delegates and I think it now As always, please feel free to get One position that is becoming embodies the aims of the ECM Forum in touch with us with any comments or available is my role as Communications more than ever. suggestions. I am particularly happy to The keynote speaker at this year’s answer any questions about running for event is Senga Robertson-Albertyn my role on the committee; I really could from the University of Dundee, UK. not recommend it enough. Senga won the 2018 Microbiology Outreach Prize for her public Rebecca Hall engagement event ‘Microbe ECM Forum Communications Motels: How to Make a Representative Healthy Poo’. It was

Microbiology Today May 19 | microbiologysociety.org 91 Membership Q&A This is a regular column to introduce our members. In this issue, we’re pleased to introduce Gerard Sheehan. G. Sheehan G.

Where are you currently based? the summer months. He offered me the teaching and research. In particular, I I am currently based in the Medical opportunity to work in his laboratory and have been highly impressed by their Mycology laboratory in the Department of I worked with postgrads on a variety of ability to inspire undergraduate students Biology at Maynooth University in Ireland. microbiology projects. I greatly valued this and to foster their careers. What is your area of specialism? experience and it increased my desire to puruse a career in microbiology. Following What do you do to relax? Host–fungal pathogen interactions and Outdoorsy stuff: I like hiking and also on from this I applied for and received a fungal virulence. play basketball at a high level in Ireland. Harry Smith Vacation Studentship from These things don’t sound very relaxing And more specifically? the Microbiology Society to work on an but they are good to clear your head and I am interested in the interplay between independent project to characterise get away from the lab. To really chill out, I fungal pathogens such as Aspergillus diseases of honey bees in Ireland. With my like a good TV series and a cuppa tea. fumigatus and Candida albicans and how time in the laboratory came confidence they (1) infect their host and (2) respond in my ability and also a love for all things What one record and luxury item to the host immune response. I mostly microbiological! would you take to a desert island? focus on the humoral response and I What are the professional challenges I would either bring a Coldplay greatest utilise insect larvae such as Galleria hits album, or preferably I would be mellonella to model infection processes that present themselves, and how do you try to overcome them? cheeky and bring my Spotify account. For in vivo. my luxury item I would have to bring a jar Working in academia certainly has its of Nutella! Tell us about your education to date advantages, but it’s the drawbacks which I studied for my BSc in Biomedical are the problem. Job security, difficulty Tell us one thing that your work Science at Maynooth University and of securing funding, lack of tenured colleagues won’t know about you. this provided me with an excellent positions, the academia/industry divide. I am lucky that we have a very close-knit background in microbiology and Maybe these will improve in years to community of postgrads in Maynooth and immunology. I am now in the final year come…but the glass is half full and I love I am extremely close with everyone in the of my PhD and I have loved the whole working in a laboratory; on a project lab, so they know me too well. One thing experience, from designing, performing which needs answers; the idea of being they won’t know about me is I was, at one and analysing experiments, to presenting your own ‘boss’ and teaching in tertiary- stage in my early life, an award-winning my work at national and international level education. Making a difference not artist. conferences. I have previously worked only in your field of expertise, but also to on projects ranging from studying the society, is really appealing to me If you weren’t a scientist, what factors affecting biofilm formation in beer would you be? lines, to blocking antibiotic resistance in What is the best part about This is a tough question, as all my college multi-drug resistant (MDR) bacteria. ‘doing science’? choices involved biology (e.g. biology and I think it’s the variety. Nothing is ever PE teaching) but if I had to stray from Where did your interest in the same and everything is fresh. I love science it would probably be something microbiology come from? working on a project and getting really practical like an electrician. During my undergraduate degree, our involved. However, it’s a great feeling to course co-ordinator at the time (now PhD finish it and move on to another exciting If you would like to be featured in supervisor; Professor Kevin Kavanagh) project. this section or know someone who lectured our class in microbiology. I may, contact Paul Easton, Head of approached him mid-way through my Who is your role model? Membership Services, at p.easton@ second year asking about the possibility I have been inspired by my lecturers microbiologysociety.org. of getting some lab experience during at university and by their dedication to

92 Microbiology Today May 19 | microbiologysociety.org Microbiology Today May 19 | microbiologysociety.org 93 Reviews

The Human Microbiota in Health composition of the indigenous microbiota; (iii) the metabolic and Disease: An Ecological and activities and relationships between host cells and microbes which influence and determine the human health; (iv) the Community-Based Approach involvement of the microbiota in human diseases; (v) the Written by Michael Wilson intervention and manipulation of the microbiota that can £148.74 ISBN 978-081534585-5 result in health effects. The book terminates reporting the The Human Microbiota in Health and most recent studies and hypotheses on possible involvements Disease is the first edition of an extraordinary updated of microbiota in other human diseases and highlighting academic resource, which provides an exhaustive description questions that still need to be answered. on the nature and diversity of the microbial communities Each chapter is magnificently illustrated, contains several inhabiting the human body. graphic charts and detailed tables, and terminates with a key The first two out of 11 chapters introduce the reader to concept list, review questions and an updated bibliography the molecular features of the host–pathogen interactions divided by topics. and the various methods used to investigate the composition Overall, the book is a valuable resource for students, of the human microbiota. Here and throughout the text, the researchers and anyone interested in the human microbiota book stresses similarities and, most importantly, differences and its impact in health and disease. of microbial data obtained through cultivation-dependent and -independent approaches. The following chapters Dr Fabio Giovannercole focus deeply on the indigenous microbiota inhabiting the Sapienza University of Rome numerous districts of the human body. In detail, each For more reviews, please visit the online issue of Microbiology chapter describes: (i) the anatomy and physiology of the Today at microbiologysociety.org/microbiologytoday. body site; (ii) the environmental determinants dictating the

94 Microbiology Today May 19 | microbiologysociety.org

Comment

together to survive inside the host. These interactions take place in the microbial Fungal flora of healthy individuals, and in the context of disease. Many infectious diseases are increasingly recognised interactions in as polymicrobial, presenting with aggressive pathologies and increased health and disease antimicrobial resistance, leading to poorer patient prognosis. Most polymicrobial interactions Courtney Kousser, Farhana Alam occur within mixed biofilms, i.e. communities of cells ensnared within and Rebecca Hall an extracellular matrix of secreted polymers. For example, the oral cavity Fungi are important eukaryotic organisms, comprised of hosts a cornucopia of fungal-bacterial more than just mushrooms and moulds, and span beyond interactions, thanks to its moist, nutrient- rich environment. The composition of environmental saprophytes. Although not all are harmful, oral biofilms is relatively similar among from the 100,000 fungal species identified to date, 300 are healthy individuals, due to the presence of a core microbiome; however, the known to impact human health. These effects can be positive microbial make-up can vary greatly or negative, and this is largely mediated by their interactions from one individual to another in cases of disease. It is estimated that around with host cells and other resident microbes. 80% of all microbial infections are in the form of biofilms. Common infection

Microbiota: microbiome + mycobiome aureus. On the other hand, fungi The microbiome is a complex community can also have negative effects. For of micro-organisms living on and within example, colonisation by Candida and humans. The mycobiome represents the Saccharomycetes is associated with fungi present within the microbiota that hepatitis B, and the presence of Candida play important roles in human health. can exacerbate disease severity and Each anatomical site has a unique delay healing of lesions in ulcerative microbial fingerprint that can vary colitis and Crohn’s disease patients. with health. For example, the intestinal Furthermore, Candida colonisation is mycobiome differs between obese and correlated with more severe instances non-obese individuals, as does the oral of acute graft-versus-host disease mycobiome of HIV-positive patients and following stem cell transplantation. healthy individuals. Candida spp. are the most prevalent A polymicrobial world fungi identified in the mycobiome Polymicrobial interactions dominate and, through competition, can act as the world around us. Just as humans a protective barrier against invading are social beings, microbes constantly Fig. 1. Microscopic image of Pseudomonas pathogens. For instance, adapted Candida form relationships with other organisms. aeruginosa attaching to Candida albicans hyphae. albicans can protect mice against These can be competitive, where Dead fungi/bacteria are stained red, fungal chitin is Aspergillus fumigatus, Pseudomonas microbes fight for resources and space; stained purple, and nucleic acids are stained green. aeruginosa, and Staphylococcus or co-operative, where they work Emily Dixon

Microbiology Today May 19 | microbiologysociety.org 95 EYES Keratitis

EARS Otitis media MOUTH Dental caries Denture stomatitis Periodontitis

sites include implanted medical devices, are currently three burns, surgical wounds and mucosal main classes of LUNGS SKIN surfaces, such as the lung epithelium in antifungals: azoles, Cystic fibrosis Burn/blast/traumatic Ventilator-associated wounds pneumonia Medical device cystic fibrosis patients. The prolonged polyenes and infections physical proximity of cells within biofilms echinocandins. The encourages both intra- and inter-species most recent antifungals, communication. anidulafungin and REPRODUCTIVE/ The interactions between fungi posaconazole, were ABDOMEN URINARY TRACT Feeding tube infections Catheter infections and bacteria can be physical, chemical developed in 2006. The Peritonitis Urinary tract infections or metabolic. Fungal hyphae can provide classification, in 2018, Gastroenteritis Vaginitis a scaffold-like structure encouraging of Candida auris as the formation of fungal–bacterial biofilms first multi-drug-resistant or provide a means of transport to fungal ‘global outbreak BONES enable bacterial dissemination into host pathogen’ highlights the Osteomyelitis tissues. Both types of organism undergo urgent need for novel FEET Diabetic foot wounds quorum sensing (QS), which is the cell- antifungal therapies. density-dependent release of signalling As most infections molecules that regulate gene expression. are polymicrobial in Fig. 2. Sites of polymicrobial infections and interactions involving fungi. The most well-studied cross-kingdom nature, this has further Courtney Kousser QS interactions are those between implications for antimicrobial Relationships between micro- C. albicans and P. aeruginosa, some of drug efficacy. For example, Streptococcus organisms can also be facilitated by which can directly affect virulence. mutans has been shown to protect host cells. Fungal interactions with the C. albicans biofilm cells from the effects immune system can influence how Antimicrobial resistance of the antifungal fluconazole, via the host responds to future microbial Fungi feature prominently in the fight secretion of polymers that sequester invasions. For instance, previous against antimicrobial resistance. There the drug. Conversely, C. albicans can sublethal infections with C. albicans enhance the tolerance of can prime the immune system; an Pseudomonas aeruginosa Escherichia coli and interaction mediated by the fungal cell S. aureus biofilm cells to wall component, β-glucan, and the the antibiotics ofloxacin phagocyte surface receptor, Dectin-1. and vancomycin, This ‘training’ leads to enhanced Quinolone signalling respectively. These co- leukocyte recruitment, cytokine Phenazines QS molecules operative interactions production and infection clearance (e.g. pyocyanin) (3-oxo-C12 homoserine lactone) suggest that antibiotic– when exposed to secondary pathogens, antifungal combination such as P. aeruginosa, or repeated • Viability Farnesol • Growth treatments would inoculation with C. albicans. • Biofilm be clinically more production Filamentation efficacious in many Future perspectives cases. Much is yet to be discovered about the myriad effects of fungi on human Yeast Candida albicans Hyphae • Disseminates to • Invade host tissues Training the health and disease. For example, secondary sites • Evade immune cells immune system there is evidence that the fungal Not all polymicrobial QS molecule farnesol can affect Fig. 3. Schematic showing the complex ways in which fungi and bacteria interactions involve human fertility, by modulating sperm can interact, using Candida albicans and Pseudomonas aeruginosa as an direct microbe–microbe motility. The impact of other microbial example. Courtney Kousser and Emily Dixon communication. communication molecules on human

96 Microbiology Today May 19 | microbiologysociety.org health and disease are yet to be Ghannoum M, The Scientist. The investigated, and who knows what Mycobiome;2016. https://www.the-scientist. Why does microbiology matter? implications these will hold for human com/features/the-mycobiome-34129 Farhana: Microbes include a hugely health. [accessed 26 February 2019]. versatile range of organisms. They Hall RA, Noverr MC. Fungal interactions with are integral to the functioning of most Further reading the human host: exploring the spectrum of ecosystems, yet we are still in our Dhamgaye S, Qu Y, Peleg AY. Polymicrobial symbiosis. Curr Opin Microbiol 2017;40:58–64. infancy in understanding their impact. infections involving clinically relevant Gram- Quinton, J. Fungal mediated innate immune Courtney: Micro-organisms coat every negative bacteria and fungi. Cell Microbiol memory, what have we learned? Semin Cell surface around us, on us, and in 2016;18:1716–1722. Dev Biol, in press. our bodies. By understanding how microbes function and how they can Courtney Kousser impact us, we can better learn how to Institute of Microbiology and Infection, School of Biosciences, work with them or fight them. University of Birmingham, Edgbaston, Birmingham B15 2TT, UK Rebecca: Studying all aspects of e [email protected] microbiology is important to enhance @cakousser our understanding and to make new Courtney Kousser is a fourth year PhD student in Dr Rebecca discoveries. Microbiology has been A Hall’s lab. Courtney’s research focuses on the interaction at the heart of identifying the basic Courtney Kousser Courtney between the deadly fungus, Rhizopus microsporus, and the principles of life for decades. Even opportunistic bacterium Pseudomonas aeruginosa within the host. She has been small pieces of the puzzle provide a member of the Microbiology Society since 2016 and won the 2018 Sir Howard clarity to the larger picture, and open Dalton Young Microbiologist of the Year Prize. new avenues of exploration. At heart, everyone is a microbiologist, they Farhana Alam might just not know it. Institute of Microbiology and Infection, School of Biosciences, What advice would you give to University of Birmingham, Edgbaston, Birmingham B15 2TT, UK someone starting out in this field? e [email protected] Farhana: Read widely and don’t limit @_farhana_alam yourself to your specific research Farhana Alam is a second year PhD student working in area. There is much to be gained Dr Rebecca Hall’s lab. Her research, in collaboration with from inter-disciplinary learning; like Farhana Alam Farhana Dr Jessica Blair, focuses on fungal–bacterial polymicrobial any other form of life, microbiology biofilms and their effects on antimicrobial resistance. does not occur in isolation! Courtney: Attend conferences, Rebecca Hall speak to the intimidating Principal Institute of Microbiology and Infection, School of Biosciences, Investigator, and step outside of your University of Birmingham, Edgbaston, Birmingham B15 2TT, UK comfort zone. You’ll gain confidence e [email protected] and become an active, well-rounded @BECKS_182 member of the community. hall-fungal-research.co.uk Rebecca: One of the best ways to get to Rebecca Hall is a current MRC-funded Career Development know people, and the field, is to go to Rebecca Hall Rebecca Award Fellow and Lecturer in Microbial Adaptation at the a conference, to hear lots of excellent University of Birmingham. Rebecca is interested in how microbes adapt to the science, ask questions and share environment of the host and the consequences this adaptation has on disease ideas. Also, the fungal community progression. She has been a member of the Microbiology Society since 2014, and may be small, but we are mighty, is a member of the Eukaryotic Division. collaborative and enjoy a good dance!

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