RESEARCH PROFILE

The focus of research is the study of bacteria in situ, in natural environments, with the aim of unraveling the mechanisms controlling responses to key environmental signals. The soil environment has been a long standing habitat of interest to detect key bacterial groups active, study mechanisms for adaptation and survival and establish population turnover in specific habitats. A fundamentally different approach is taken from traditional in vitro work with environmental isolates, as we follow gene expression in situ, this dictates the direct extraction of both cells and molecules. We have pioneered methods for direct extraction of DNA and RNA from soil and immunomagnetic capture of bacteria from soil. One current aim is to apply metaproteomics in addition to current metagenomic studies in order to gain a profile of uncultured groups and link this to their activity. Recent developments involved the discovery that carbon flow below ground can be disrupted by soil microfauna and led to an improved understanding of how nutrients flow between plants and microorganisms. Soil is a major reservoir of microbial pathogens and in situ analysis of selected environments resulted in a crucial revelation that pollution will drive selection for adaptive genes already rapidly evolving in bacteria found in hospitals and farms where biocides and antibiotics are in frequent use. Inevitably this leads to increased dissemination of antibiotic resistance genes which will also occur if pathogens survive for extended periods in the environment. We have also demonstrated the latter and been able to define specific reservoirs of both genes and pathogens in relation to environmental selection, including hot spots for antibiotic resistance genes, and sources of Salmonella species and Mycobacterium bovis.

Research with epidemiologists and mathematicians has featured studies on the understanding of spread of Mycobacterium bovis (Orin Courtenay) and salmonellae-amoebae interactions (Nigel Burroughs) in the agricultural environment and the food chain and shown significantly that pathogens reservoirs exist in the environment outside of the host and sometimes within amoebae and present a potential infection reservoir (Young et al., 2005; Gaze et al., 2003, for mycobacteria and salmonellae respectively). Joint projects between EMHW and the Mathematics Institute (Nigel Burroughs) have shown that gene flow in the environment is extensive for bacterial populations and is likely to be promoted by availability of nutrients and predators such as amoebae. This will increase transfer of drug resistance genes as selection with disinfectants is currently selecting for resistance plasmids and gene cassettes in biofilms and slurries (NERC funded, Gaze et al., 2005). Additional research has focused on the ecological roles of antibiotics and evidence has been reported to demonstrate conditions in soil conducive to expression of antibiotic gene clusters using reporter gene fusions and by detection of mRNA extracted from soil (Anukool et al., 2004). Population ecology of bacteria in soil has been a continuing interest and following many years of work studying the dynamics of phage-host interactions in soil, mathematical models were developed firstly with Nigel Burroughs and currently with Matt Keeling and Jonathan Read. In the latter we are working on simulations to compare the dynamics in liquid, on agar surfaces and in soil. This will lead to understanding interactions in a heterogeneous environment where connectivity of populations is complex and difficult to predict. Soil provides a reservoir for bacterial pathogens and understanding the epidemiology of exotic bacteria in soil is pertinent in understanding the spread of zoonotic infections.

A 'systems' approach is currently being taken to elucidate the global metabolic switch which occurs prior to antibiotic production in order to understand one of the important adaptive features for selected soil bacteria including streptomycetes (the most commercially important group for exploitation). The project is part of the SysMO programme (www.sysmo.net) with BBSRC funding UK projects, and is coordinated by Prof Liz Wellington and involves a multidisciplinary team from Biological Sciences and Warwick Systems Biology Centre. Antibiotics are made during the second phase of growth when there is a transition in metabolism from primary to secondary metabolism. Primary metabolism is growth related and involves all the normal cellular activities associated with cell growth and division. Whereas secondary metabolism is non-growth linked and is non-essential but many important activities occur during this phase which help the bacterium survive. One of these activities is antibiotic production and is widespread in streptomycetes found in most soils. These bacteria have a fascinating life history and are abundant producers of biologically active compounds many of which have been exploited for their anti-tumour, anti-bacteria and anti-fungal activity. Our research will improve our understanding of how these bacteria regulate the transitions from primary to secondary metabolism and provide mathematical models to simulate the metabolic switch of life styles. The approach is regarded as a 'systems' analysis where a model is built of the whole metabolism and it can predict outcomes that will not have been determined previously by experimental methods. A range of modelling tools will be provided and these will be available for use with many other projects involved in a systems approach. The fuller understanding of the metabolic switch and the elucidation of how and why certain antibiotics are made under defined growth conditions will be vital for the exploitation of these bacteria. Many tools are available to manipulate bacterial genomes and with an understanding of the metabolism it will be possible to manipulate growth in order to produce novel antibiotics.

CURRENT RESEARCH PROJECTS

• Tuberculosis epidemiology and novel transmission routes in rural Tanzania, with Dr Orin A Courtenay - Biological Sciences, Funded by: National Institutes of Health, Project Start Date: 01/08/2010 Project End Date: 31/07/2015
• Development of Metaproteomics for In-situ Investigation of Microbial Activity both in Vivo and in Soil and Faeces, Funded by: BBSRC, Project Start Date: 01/04/2010 Project End Date: 31/03/2014
• METAEXPLORE- Metagenomics for bioexploration- Tools and application, Funded by: EU, Project Start Date: 01/01/2009 Project End Date: 31/12/2013
• Studentship 'In situ analysis of the microbial community associated with footrot of sheep', Funded by: Pfizer Limited, Project Start Date: 01/10/2008 Project End Date: 30/09/2012
• Tuberculosis epidemiology and novel transmission routes in rural Tanzania (Year 2), Funded by: University of California, San Francisco, Project Start Date: 01/07/2011 Project End Date: 30/06/2012
• The ecology of protist associated human pathogens, Funded by: NERC, Project Start Date: 01/03/2011 Project End Date: 31/05/2012
  
  

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SELECTED PUBLICATIONS

• Thomas, Louise, David A Hodgson, Alexander Wentzel, kay Nieselt, Trond, E, Ellingsen, Jonathan Moore, Edward R Morrissey, Roxane Legaie, the STREAM consortium, Wolfgang Wohlleben, Antonio Rodrigues-Garcia, Juan F Martin, Nigel J Burroughs, Elizabeth M.H. Wellington and Margaret C M Smith(2012) 'Metabolic switches and adaptations deduced from the proteomes of Streptomyces coelicolor wild type and phoP mutant grown in batch culture' Molecular and Cellular Proteomics 11 (2), (1535-9476)
• Tsibidisa, G.D., Burroughs, Nigel J., Gazec, W. Wellington, E. M.H.(2011) 'Semi-automated Acanthamoeba polyphaga detection and computation of Salmonella typhimurium concentration in spatio-temporal images' Micron 42 (8), 911 - 920 (0968-4328) [article]
• Travis Emma R.; Gaze William H.; Pontiroli Alessandra; et al.(2011) 'An Inter-Laboratory Validation of a Real Time PCR Assay to Measure Host Excretion of Bacterial Pathogens, Particularly of Mycobacterium bovis' PLoS One 6 (11), (1932-6203)
• Gaze William H.; Zhang Lihong; Abdouslam Nouradin A.; et al.(2011) 'Impacts of anthropogenic activity on the ecology of class 1 integrons and integron-associated genes in the environment' ISME Journal 5 (8), 1253 - 1261 (1751-7362)
• Anukool Usanee; O'Neill Colette E.; Butr-Indr Bordin; et al.(2011) 'Meticillin-resistant Staphylococcus aureus in pigs from Thailand' International Journal Of Antimicrobial Agents 38 (1), 86 - 87 (0924-8579)

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