ANNUAL CONFERENCE 14-17 April 2014 Arena and Convention Centre, Liverpool ABSTRACTS SGM ANNUAL CONFERENCE APRIL 2014 ABSTRACTS (LI00Mo1210) – SGM Prize Medal Lecture (LI00Tu1210) – Marjory Stephenson Climate Change, Oceans, and Infectious Disease Prize Lecture Dr. Rita R. Colwell Understanding the basis of antibiotic resistance University of Maryland, College Park, MD, USA as a platform for early drug discovery During the mid-1980s, satellite sensors were developed to monitor Laura JV Piddock land and oceans for purposes of understanding climate, weather, School of Immunity & Infection and Institute of Microbiology and and vegetation distribution and seasonal variations. Subsequently Infection, University of Birmingham, UK inter-relationships of the environment and infectious diseases Antibiotic resistant bacteria are one of the greatest threats to human were investigated, both qualitatively and quantitatively, with health. Resistance can be mediated by numerous mechanisms documentation of the seasonality of diseases, notably malaria including mutations conferring changes to the genes encoding the and cholera by epidemiologists. The new research revealed a very target proteins as well as RND efflux pumps, which confer innate close interaction of the environment and many other infectious multi-drug resistance (MDR) to bacteria. The production of efflux diseases. With satellite sensors, these relationships were pumps can be increased, usually due to mutations in regulatory quantified and comparatively analyzed. More recent studies of genes, and this confers resistance to antibiotics that are often used epidemic diseases have provided models, both retrospective and to treat infections by Gram negative bacteria. RND MDR efflux prospective, for understanding and predicting disease epidemics, systems not only confer antibiotic resistance, but altered expression notably vector borne diseases. The water borne disease, cholera influences the ability of the bacterium to infect its host and to form a can be predicted by monitoring sea surface temperature, salinity, biofilm. I will illustrate our studies on the mechanisms of antibiotic rainfall, and chlorophyll, the latter as a tag for phytoplankton that resistance - from phenotype to genotype and studies on gene precede zooplankton in abundance in coastal and river waters, regulation - in isolates of Salmonella from animals and a unique set since zooplankton carry cholera bacteria as a component of their of clinical isolates collected over the course of a complex infection natural flora. Recent studies of the cholera epidemic in Haiti provide in which the patient received numerous antibiotics, and yet died evidence that an early warning system for infectious diseases can, with a disseminated MDR infection. I will also describe how some indeed, be developed, providing a powerful tool for protecting public of the information we have obtained informs those involved in drug health and, more importantly, for measuring effects of climate discovery programmes. change on human health. Genomic analyses of Vibrio cholerae isolated globally have provided additional evidence of multiple sources of cholera epidemics. Furthermore, metagenomic data show (LI00We1210) – Fleming Prize Lecture more than one pathogen in clinical samples collected during cholera Multiple personalities of RNA polymerase active outbreaks. centre Nikolay Zenkin (LI00Mo1735) – Peter Wildy Prize for Centre for Bacterial Cell Biology,Newcastle University, Newcastle- Microbiology Education upon-Tyne, UK Science communication: a communicable Transcription in all living organisms is accomplished by highly disease? conserved multi-subunit RNA polymerases (RNAP). The view on the functioning of the active centre of RNAP has transformed recently Stephen Curry with the finding that a conserved flexible domain near the active Professor of Structural Biology, Director of Undergraduate Studies centre, the Trigger Loop (TL), directly participates in the catalysis Department of Life Sciences, Imperial College, London UK of RNA synthesis and serves as a major determinant for fidelity “I will share my experiences of science — such as they are and of transcription. It also appeared that the Trigger Loop is involved as frankly as I can.” These are the words I wrote in my very first in the unique ability of RNAP to exchange catalytic activities of the blogpost in 2008. They represent my mission statement but also, I active centre. In this phenomenon the Trigger Loop is replaced now realise, mark the beginning of a kind of infection that has had by a transcription factor which changes amino acid content and, unexpected sequelae. I had meant only to start writing about what as a result, catalytic properties of the active centre. A number it was like to work as a scientist in 21st century Britain but was transcription factors that act through substitution of the Trigger surprised to find that my blog frequently took me outside the usual Loop suggest that RNAP has several different active centres to boundaries of a scientific life. Once you look up from the bench you choose from in response to external or internal signals. soon find many interesting and important cultural growths that are not confined to petri dishes or baffled flasks. There are issues of careers, of funding, of public perceptions and of the politics inside and outside science, all of which affect its relationship with the rest of society. Many of us encounter and think about these matters on a regular basis; but doing something about them is easier than you might imagine. In my talk I would like to describe the pathology of my particular infection, which I believe to be mostly benign. I hope I might also be able to infect some of the members of the audience. 2 Please note: Abstracts are published as received from the authors and are not subject to editing. SGM ANNUAL CONFERENCE APRIL 2014 ABSTRACTS LI01 LI01Mo0945 10 questions in virology Offered paper – Recombination in Enteroviruses is a Biphasic Process Involving the Generation LI01Mo0900 of Greater-than Genome Length ‘Imprecise’ Virus ecology: studying animal reservoirs to Intermediates understand viral emergence Andrew Woodman1, Kym Lowry2, David Evans1 1 Christian Drosten School of Life Sciences, The University of Warwick, Coventry, UK, 2Biosecurity Sciences Laboratory, Queensland, Australia Institute of Virology, University of Bonn, Germany Members of the Picornaviridae have error prone polymerases, short Ten years after the SARS epidemic, zoonotic and emerging viruses replication cycles, and high yields that together contribute to genetic have become a growing field of research. Some remarkable novel diversity. However, far greater genetic variation is achieved by chance virus descriptions in animals have demonstrated how ignorant we recombination events than is possible in a single round of genome are of the diversity of viruses around us. In our efforts to delineate replication. Genetic recombination is believed to be due to a ‘copy-choice’ viral origins we may have to re-asess our concept of reservoir. In mechanism and, at present, it is suggested that the RNA dependent RNA many instances, we are mixing up ecological and epidemiological polymerase pauses or terminates at certain RNA sequence motifs, or implications of viral evolution. Among the biggest challenges in this secondary structures, promoting template switching. field is the integration of the concepts of virus-host codivergence, We have developed a system that exploits two partially replication and viral host switching. In addition, assessments of viral reservoirs competent parental genomes to specifically select early with the intention to predict future pandemic threats would have to recombination products from a co-transfected cell population. All take into account important host and virus traits which cannot be viable progeny are recombinants and, strikingly, the majority contain predicted merely from virus genes. For example, we need to know in-frame duplications of up to ~400 nt. at the recombination junction. whether there are hosts which have a higher propensity to carry Mutagenic nucleoside analogues can lead to ‘error catastrophe’ broader spectra or higher concentrations of viruses, potentially amongst an enterovirus population. Interestingly, we have evidence without being affected. Among the viruses borne in such reservoirs, to show that sub-lethal levels of the mutagenic compounds lead to there may be some that are more promiscuous in their choice of a significant enhancement of recombination frequency. In contrast, a hosts than others, potentially due to the conservedness of their high fidelity polymerase mutant significantly reduces recombination receptor structures or the way they interfere with conserved- or frequency. This provides insights into the characteristics of the not-so-conserved immune properties. A synopsis of available polymerase that are important for recombination and implies that approaches demonstrates how much work needs to be done before antiviral therapy may, in addition to selecting for drug resistance, we will be able to assess functional, rather than genetic diversity of influence viral recombination in co-infected patients. reservoir-borne viruses LI01Mo0930 LI01Mo1000 Can we track viruses in real time, in the real Offered paper – Harnessing the cellular world? microRNA machinery to probe norovirus tropism Jonathan Read Lucy Thorne, Ian Goodfellow University of Liverpool, Liverpool, Merseyside, UK University of Cambridge,