Plasmids as AMR vectors. MRC GW4 BioMed DTP PhD studentship 2025/26

About the GW4 BioMed2 Doctoral Training Partnership

The partnership brings together the Universities of Bath, Bristol, Cardiff (lead) 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, with opportunities to participate in interdisciplinary and ‘team science’. The DTP already has over 90 studentships over 6 cohorts in its first phase, along with 58 students over 3 cohorts in its second phase.

Project Information

Research Theme:

Infection, Immunity, Antimicrobial Resistance & Repair

Summary

Antimicrobial resistance (AMR) is rising to dangerously high levels causing a global health crisis. To develop strategies to combat AMR, we need to know how AMR genes are spreading. Plasmids as ubiquitous mobile genetic elements are key players of AMR spread. Antibiotics make carry AMR plasmids beneficial to their bacterial hosts and therefore drive plasmid prevalence and evolution. This project will investigate the evolution of highly transmissible AMR plasmids that can spread resistance within and between microbiomes. This will be done by targeted experiments and investigations of complex microbiomes using plasmid genomics and network analysis.

Project Description

The widespread use of antibiotics in clinical and agricultural settings has resulted in the rapid evolution and spread of antibiotic resistance causing a major health crisis (1). Bacteria can gain resistance to antibiotics through mutations or by taking up resistance genes (2). Plasmids play a key role in the spread of antimicrobial resistance (AMR) genes (3) because of their ability to transfer between different bacteria (4). The range of different bacterial hosts that plasmids interact with, i.e. plasmid generalism, is therefore crucial for the spread of AMR. There is evidence that antibiotic pressure can enhance plasmid generalism and this may not only facilitate the spread of the AMR genes under selection, but also may allow additional AMR genes to hitchhike along with the generalist plasmids (5). This could then lead to the spread of multi-drug resistant plasmids throughout microbial communities and, more worryingly, between environmental, agricultural and clinical microbiomes, a threat acknowledged in the OneHealth concept (2). AMR plasmid spread could be mitigated if plasmid generalism is a transient effect, reducing when antibiotic selection is lowered. However, it is unclear if this is the case. Plasmids can evolve incredibly quickly (6), and continued exposure to multiple hosts may lead to the evolution of

plasmids that are even more successful at transmitting within microbiomes (7). Exposure to even a single antibiotic may lead to the evolution of plasmids that are highly infectious vectors of AMR genes in general.

This project aims to determine how plasmids become transmissible AMR vectors. It will be experimentally tested how environmentally relevant antibiotic exposure regimes shape plasmid generalism and determine the molecular/functional changes on the plasmid. The project will further investigate the spread of AMR plasmids in complex communities (host-plasmid networks) and to pathogens combined with theoretical modelling.

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