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Trade offs between beta-lactam/beta-lactamase inhibitor resistance and fitness in Enteric bacteria

Project Description

This studentship is open to Thai applicants only.

Beta-lactams are the most widely prescribed antimicrobial class worldwide. Resistance is primarily caused when bacteria produce beta-lactamase enzymes, of which there are many different types. There are several clinically available beta-lactamase inhibitors; chemicals which block beta-lactamase mediated resistance, therefore allowing a partner beta-lactam to regain function. Key examples are amoxicillin/clavulanate and piperacillin/tazobactam, which are mainstay combinations in the UK; ceftazidime/avibactam and meropenem/vaborbactam, which have recently been introduced into clinical practice; and several experimental inhibitors in various stages of development.
The aim of this project is to investigate mechanisms of resistance to these different combinations in two key human pathogens: Escherichia coli and Klebsiella pneumoniae. You will investigate whether different clinical isolates have different potentials for generating resistance, and identify the mechanisms involved. You may use structural biology and enzyme analysis of resistance is a property of the beta-lactamase; you will use functional genomics approaches to study mechanism of resistance if chromosomal. You will benefit from access to clinical, animal and environmental isolates from the UK and Thailand, collected as part of two large consortium projects.
By developing novel flow cytometry approaches, you will also investigate whether resistance comes with a measurable fitness cost, and if different resistant variants of different background strains has a greater or lesser fitness, suggesting those backgrounds most likely to yield successful resistant strains that might circulate in the population.
The project will suit someone with a microbiology, molecular biology or biochemistry background, who wants to work in an inter-disciplinary team to understand this important clinical problem

Funding Notes


This is 3 year fully-funded PhD studentship funded by the University of Bristol.
Stipend: £14,925. Full overseas fees covered, Research costs covered

When applying please select Faculty of Life Sciences, School of Cellular and Molecular Medicine., 3 year PhD.

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