The Bloomsbury Colleges | PhD Studentships | Studentships 2016 | Longterm trends and mechanisms of antimicrobial resistance in bacterial pathogens; an extensive, multi species genome based approach (RVC) & (LSHTM)
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Longterm trends and Mechanisms of Antimicrobial Resistance in Bacterial Pathogens; an extensive, multi species genome based appoach

Principle Supervisor: Professor Stuart W.J. Reid (RVC)

Co-Supervisor: Professor Nick Thomson (LSHTM)

Rationale: Antimicrobial resistance (AMR) of bacterial infections is one of the greatest health threats facing society. The Review on Antimicrobial Resistance, established by the UK Government, estimated that resistant infections could cause 10 million human deaths per year globally by 2050, and cost more than 100 trillion USD. It is also of concern for veterinary science, as treatment failure due to resistant infections is a health and welfare issue for animals, and the morbidity and mortality associated with resistance leads to increased production costs and public health risks.

AMR is an ancient and naturally occurring phenomenon. However, the discovery and widespread use of antimicrobials has created selection pressures that have contributed to the evolution of resistance and its global dissemination. There is a critical need to evaluate how AMR has changed in response to these pressures, not only in its molecular mechanisms, but also in the mobile genetic elements (MGEs), such as plasmids, which carry the resistance. The Murray collection provides a unique opportunity to dissect this issue, comprising several hundred bacterial isolates from key pathogen groups collected prior to the widespread use of antimicrobials (1). Nearly half of these isolates have been recently sequenced, providing a unique resource.

Understanding where AMR arises, and how it spreads within and between populations, is essential information if effective control strategies are to be formulated. Our previous work has demonstrated that, for a particular subtype of Salmonella, contrary to established tenets, the local animal population was highly unlikely to be the major source of AMR or indeed of the bacterium for humans (2). However, the dynamics of AMR are likely to vary for different organisms and in different ecological and geographical settings; the opportunity of exploring trends and patterns of AMR in different populations, for which we have extensive and long term genomic datasets, will provide important new insights into different pathogens as well as into the common mechanisms and dynamics they may

share. Furthermore, macro population level impacts on animal demography such as the foot-and-mouth disease outbreak in 2001, and more recently bovine tuberculosis (4), provide important epidemiological, ecological and temporal watersheds for comparative analysis of the spread of pathogens and resistance determinants in perturbed populations.

Aims & objectives:

  1. To evaluate how AMR and the MGEs carrying AMR have changed following the discovery and extensive use of antimicrobial drugs
  2. To explore the diversity of plasmids within current genomic datasets using existing plasmid replicon typing schemes, and develop new primer sequences to identify any plasmids not covered by current schemes
  3. To identify epidemiological barriers, such as host species or bacterial subtype, to the cross-movement of plasmids
  4. To identify associations between replicon typing and phenotypic AMR
  5. To investigate the epidemiological trends and patterns of AMR in multiple animal species over a 20 year period, using phenotypic AMR and previously identified replicon associations
  6. To investigate the impact of unrelated large-scale animal health events on AMR trends in bacterial populations in animals

Candidate Requirements

The appointee will be expected to work with supervisors and collaborators on-site at the Royal Veterinary College, the London School of Hygiene and Tropical Medicine, the Wellcome Trust Sanger Institute, and the University of Cambridge.

Key References:

  1. Baker, K.S., Burnett, E., McGregor, H. et al (2015) The Murray collection of pre-antibiotic era Enterobacteriacae: a unique research resource. Genome Med. 7:97.
  2. Mather, A.E., Reid, S.W.J., Maskell, D.J. et al (2013) Distinguishable epidemics of multidrug resistant Salmonella Typhimurium DT104 in different hosts. Science 341:1514-1517.
  3. Carattoli, A., Bertini, A., Villa, L. et al (2005) Identification of plasmids by PCR-based replicon typing. J Microbiol Methods 63:219-228.
  4. Carrique-Mas, J.J., Medley, G.F., Green, L.E. (2008) Risks for bovine tuberculosis in British cattle farms restocked after the foot and mouth disease epidemic of 2001. Prev Vet Med 84:85-93

Further details about the project may be obtained from:

Principle Supervisor: Professor Stuart W.J. Reid (swjreid@rvc.ac.uk)

Co-Supervisor: Professor Nick Thompson (nrt@sanger.ac.uk)

Further information about PhDs at the Royal Veterinary College is available from:

http://www.rvc.ac.uk/study/postgraduateĀ  or by e-mail researchdegrees@rvc.ac.uk

Application forms and details about how to apply are available from:

http://www.rvc.ac.uk/study/postgraduate/phd/how-to-apply

Closing date for application is:

Wednesday 17th February 2016