Predicting the Persistence of Resistance Across Environments

Environment

Interventions

Research Project: 2017-05-01 - 2020-04-30
Total sum awarded: €349 692

Antimicrobial resistance poses a serious challenge to health care worldwide. Attempts to control resistance by stopping antimicrobial use have met with mixed success. Failures of a critical assumption underlying such strategies – that resistant strains suffer a disadvantage in the absence of drug (the “cost of resistance”) – may be responsible for difficulties in controlling resistance by cessation of drug use. In particular, resistance mutations may be cost free, and hence persist, in some environments or on some genetic backgrounds. Furthermore, even when resistance is initially costly, compensatory evolution – the accumulation of mutations that restore fitness while maintaining resistance – may allow resistant strains to persist. Using two pathogenic bacterial species, we propose to undertake a systematic study of the costs of resistance across multiple genetic backgrounds, as well as across a variety of relevant conditions across the human-animal-environment axis. Moreover, we will determine whether resistant pathogens take the same, or different, routes to compensation in different environments. Taking advantage of evolutionary theory, we will determine the feasibility of predicting the costs of resistance in one environment using information from another environment, which would aid in predicting the persistence of resistant strains using limited information from laboratory studies. The proposed work will provide crucial information for public health policy on strategies for controlling resistance.

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  • Alex Wong, Carleton University, Canada (Coordinator)
  • Claudia Bank, Instituto Gulbenkian de Ciência, Portugal (Partner)
  • Thomas Bataillon, University of Aarhus, Denmark (Partner)
  • Isabel Gordo, Instituto Gulbenkian de Ciência, Portugal (Partner)
  • Rees Kassen, University of Ottawa, Canada (Partner)

Antimicrobial resistance poses a serious challenge to health care worldwide. One common approach to tackling resistance is to stop using a particular antimicrobial for a period of months or years, in the hope that resistance will decrease. However, such attempts to control resistance by stopping antimicrobial use have met with mixed success. Failures of a critical assumption underlying such strategies – that resistant strains suffer a disadvantage in the absence of drug (the “cost of resistance”) – may be responsible for difficulties in controlling resistance by cessation of drug use. The PREPARE consortium was convened to develop an experimental and theoretical framework for understanding, and ultimately predicting, the conditions under which resistance will persist. Specifically, we set out to address the roles of host genetic background and environment in determining the costs of resistance. That is, we asked whether there are particular environments, or particular bacterial strains, in which we would expect to see resistance persist. We found that there are indeed strains, environments, and combinations thereof, where resistance confers no cost. This suggests that. resistance could persist in some real-world settings, even when antimicrobial usage has been stopped or paused. Unfortunately, we found that it is very difficult to predict which environments or strains might act as reservoirs for resistance. Novel mathematical models do show promise in increasing our ability to predict persistence. The ability to make such predictions will assist policy-makers in formulating strategies for controlling the spread of resistance.

Call

2016 - Transmission Dynamics