The spread of antibiotic resistance in bacteria-plasmid networks

Lead Research Organisation: UNIVERSITY OF EXETER
Department Name: Biosciences

Abstract

Antimicrobial resistance (AMR) is rising to dangerously high levels causing a global health crisis by threatening our ability to treat common infectious diseases. The intensive use of antibiotics for human treatment and in farming has dramatically increased the frequency of resistance with hotspots found in hospitals and many parts of the environment.

Plasmids, mobile genetic elements, have a crucial role in spreading antimicrobial resistance. They can carry resistance against antibiotics and pass this on to bacteria. Antibiotics make such AMR carrying plasmids beneficial to their bacterial hosts. This is likely to change coevolutionary dynamics between plasmids and their hosts, resulting in plasmids becoming more prevalent and associated with a higher number of different bacteria. This fundamentally changes the network structure of interacting bacteria and plasmids and likely increases the spread of novel antibiotic resistance across microbial communities.

With a series of experiments using simple and naturally complex microbial communities, I will determine the long-term impact of antibiotic exposure on plasmids and their bacterial hosts. I will also investigate emerging networks between plasmids and bacteria with novel methods. This experimental work, combined with theoretical approaches, will help predict the long-term impact of antibiotic pressure on the spread of antibiotic resistance across microbial communities and pathogens. The work will be conducted at the University of Exeter in collaboration with experts Alvaro San Millan (Madrid), Eva Top and Thibault Stalder (Idaho).

Technical Summary

Plasmids, as ubiquitous extrachromosomal elements, have a crucial role in the spread of antimicrobial resistance (AMR). Antibiotic pressure makes AMR carrying plasmids beneficial to their bacterial hosts. This is likely to change coevolutionary dynamics between plasmids and their hosts, resulting in plasmids becoming more prevalent and associated with a higher number of bacterial hosts. This fundamentally changes the network structure of interacting bacteria and plasmids and likely increases the spread of novel antibiotic resistance across microbial communities. With a series of experiments using culturable simple and naturally complex microbial communities, I will determine the long-term impact of antibiotic exposure on plasmid and host fitness and the structure of host-plasmid networks. I will further test whether networks that emerge under antibiotic pressure increase the spread of novel resistance genes. This experimental work, combined with modelling approaches, is vital to predicting the long-term impact of antibiotic pressure on the spread of antibiotic resistance to pathogens.

Publications

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