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ERC

RESISTEVO Report Summary

Project ID: 281591
Funded under: FP7-IDEAS-ERC
Country: United Kingdom

Final Report Summary - RESISTEVO (The evolution of antibiotic resistance: integrating molecular mechanisms of resistance and evolutionary context)

Antibiotic resistance in pathogenic bacteria has emerged as a fundamental threat to human health and welfare. The goal of the RESISTEVO project was to investigate the evolutionary drivers of antibiotic resistance using controlled, in vitro experiments where evolution can be observed in real time. RESISTEVO measured how antibiotic resistance changes bacterial fitness in both the presence and absence of antibiotics using novel, large-scale experiments that allowed this fundamental evolutionary parameter to be measured at an unprecedented scale. RESISTEVO then determined the biochemical and genetic mechanisms that shape the fitness effects of antibiotic resistance. Achieving these two objectives allowed RESISTEVO to answer a simple question: when will natural selection favour the spread and loss of antibiotic resistance? One of the key findings of these experiments was to demonstrate that antibiotic resistance usually carries a fitness cost, so that natural selection will favour the loss of resistance once the use of antibiotic is discontinued. The second component of RESISTEVO then asked how resistance can be maintained in pathogen populations given this cost. Our key finding in this area was to demonstrate that continued antibiotic use and selection to minimise the fitness cost of resistance interact to maintain resistance in pathogen populations. Put simply, natural selection ensures that the stability of antibiotic resistance in pathogen populations increases with the frequency or intensity of antibiotic use. In the final component of RESISTEVO we investigate how genome structure influences the evolution of novel bacterial traits, such as resistance to a new antibiotic. The key finding of our work in this area was to demonstrate that genes that exist as duplicate copies in the genome provide the evolutionary fuel for evolving new traits. Antibiotic resistance genes are often carried in on multi copy plasmids, and these findings help to explain why plasmids have played such an important role in the spread of resistance in pathogen populations. In summary, RESISTEVO has produced fundamentally new an important insights into how natural selection drives the origin, spread and maintenance of antibiotic resistance genes in bacterial populations. Looking forward, it will be possible to apply the insights from this research program to design improved treatments strategies for preventing the spread of resistance in clinical settings.

Reported by

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
United Kingdom
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