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GW4 BioMed2 MRC DTP PhD project: Evolution of antimicrobial resistance in bacterial microbiomes


   Department of Life Sciences

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  Dr Brian Jones  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

This project is one of a number that are in competition for funding from the GW4 BioMed2 MRC Doctoral Training Partnership which is offering up to 20 studentships for entry in October 2023.

The DTP brings together the Universities of Bath, Bristol, Cardiff and Exeter to develop the next generation of biomedical researchers. Students will have access to the combined research strengths, training expertise and resources of the four research-intensive universities. More information may be found on the DTP’s website.

SUPERVISORY TEAM:

  • Dr Brian Jones (lead), University of Bath, Department of Life Sciences
  • Prof Eshwar Mahenthiralingam, Cardiff University, School of Biosciences
  • Prof Mark Sutton, United Kingdom Health Security Agency, Porton Down
  • Dr Tiffany Taylor, University of Bath, Department of Life Sciences

THE PROJECT:

Background

Biocides are antimicrobial agents used extensively in healthcare settings as antiseptics or disinfectants. The increasing use of biocides has been driven by efforts to reduce antibiotic use and the Covid-19 pandemic. However, evidence is accumulating that biocides can select for undesirable traits in bacterial pathogens, including antibiotic resistance. For example, our work with urinary tract pathogens has shown that biocide exposure in Klebsiella pneumoniae can select for mutations conferring resistance to colistin (an antibiotic of last resort). The genes found to acquire mutations following biocide exposure include phoPQ and pmrAB, which are also linked to immune evasion during infection. We have also identified mutations related to biocide adaptation in clinical isolates of Proteus mirabilis, showing that these traits arise in the clinical environment. This raises the possibility that the increased use of biocides in hospitals could lead to the emergence of bacterial strains that are both more virulent and more difficult to treat.

Aims & Objectives 

Bacteria predominantly exist as polymicrobial communities, or microbiomes, in many clinically relevant habitats. However, it is unclear how biocide exposure contributes to the emergence of antimicrobial resistance in members of these microbiomes. This project will answer important questions regarding the role of biocide exposure in the evolution of antimicrobial resistance within bacterial communities, using a clinically relevant model of polymicrobial catheter-associated infection. This model provides a tractable microbiome system facilitating the application of directed evolution, genomic, and metagenomic approaches to understand evolution of antimicrobial resistance.

Objective 1 - Impact of biocide exposure on community dynamics and selection of antimicrobial resistance. Polymicrobial models of catheter associated UTI will be used to simulate antiseptic treatment with biocides. The response of bacterial communities will be evaluated through phenotypic and genomic, and metagenomic characterisation of populations recovered pre and post treatment. This will allow us to understand the impact of biocide exposure on community members and if mutations relevant to biocide tolerance and/or antibiotic resistance arise in these microbiomes.

Objective 2 - Biocide exposure and plasmid transfer. The transfer of plasmids between bacterial species is a key mechanism in the dissemination of antibiotic resistance. Catheter microbiome models and simulated biocide treatment scenarios will be used to understand the impact of biocide exposure on transfer of plasmids encoding antibiotic resistance determinants between community members. This will include plasmids encoding resistance mechanisms already linked to biocide adaptation, such as colistin resistance, as well as plasmids encoding unrelated resistance genes.

Objective 3 - Biocide adaption and modulation of virulence. The adaptation of bacterial pathogens to biocides has been linked with mutations that are also potentially relevant to virulence, and in particular the evasion of antimicrobial peptides relevant to the innate immune response. We will use our novel insect models of infection to understand if adaptation to biocides in microbiome models modulates the virulence of community members.

Student Ownership

The student will be encouraged and supported to take ownership of the project from the outset. The supervisory team will enable the student to take the lead on experimental design and the specific focus of work in each objective. Initial "prep-period" activities and training will enable the student to more specifically define the research questions and lead implementation of experiments to test hypotheses they develop.

REQUIREMENTS:

Applicants must have obtained, or be expected to obtain, a First or Upper Second Class UK Honours degree, or the equivalent qualifications gained outside the UK, in an area appropriate to the skills requirements of the project. Academic qualifications are considered alongside significant relevant non-academic experience.

Non-UK applicants will also be required to have met the English language entry requirements of the University of Bath.

ENQUIRIES AND APPLICATIONS:

Informal enquiries are welcomed and should be directed to Dr Brian Jones on email address [Email Address Removed].

Formal applications must be submitted direct to the GW4 BioMed2 DTP using their online application form.

A list of all available projects and guidance on how to apply may be found on the DTP’s website. You may apply for up to 2 projects.

APPLICATIONS CLOSE AT 17:00 (GMT) ON 2 NOVEMBER 2022.

IMPORTANT: You do NOT need to apply to the University of Bath at this stage – only those applicants who are successful in obtaining an offer of funding from the DTP will be required to submit an application for an offer of study from Bath.


Funding Notes

Candidates may be considered for a 4-year GW4 BioMed2 MRC DTP studentship covering tuition fees, a stipend (£17,668 p/a in 2022/23) and a Research & Training Support grant of between £2,000 and £5,000 p/a dependent on project requirements. Studentships are open to both Home and International students; however, International applicants should note that funding does NOT cover the cost of a student visa, healthcare surcharge and other costs of moving to the UK. In line with guidance from UK Research and Innovation (UKRI), the number of awards available to International candidates will be limited to 30% of the total.

References

• Garratt I, et al. Long-term exposure to octenidine in a simulated sink-trap environment results in selection of Pseudomonas aeruginosa, Citrobacter and Enterobacter isolates with mutations in efflux pump regulators. Appl Environ Microbiol. 2021 Mar 5:AEM.00210-21.
• Wand ME, et al. SmvA is an important efflux pump for cationic biocides in Klebsiella pneumoniae and other Enterobacteriaceae. Sci Rep. 2019 Feb 4;9(1):1344.
• Pelling et al 2019. De-repression of the smvA efflux system arises in clinical isolates of Proteus mirabilis and reduces susceptibility to chlorhexidine and other biocides. Antimicrob Agent Chemother 63:e01535-19.

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