Within-host dynamics shape antibiotic resistance in commensal bacteria

Abstract

The spread of antibiotic resistance, a major threat to human health, is poorly understood. Simple population-level models of bacterial transmission predict that above a certain rate of antibiotic consumption in a population, resistant bacteria should completely eliminate non-resistant strains, while below this threshold they should be unable to persist at all. This prediction stands at odds with empirical evidence showing that resistant and non-resistant strains coexist stably over a wide range of antibiotic consumption rates. Not knowing what drives this long-term coexistence is a barrier to developing evidence-based strategies for managing the spread of resistance. Here, we argue that competition between resistant and sensitive pathogens within individual hosts gives resistant pathogens a relative fitness benefit when they are rare, promoting coexistence between strains at the population level. To test this hypothesis, we embed mechanistically explicit within-host dynamics in a structurally neutral pathogen transmission model. Doing so allows us to reproduce patterns of resistance observed in the opportunistic pathogens Escherichia coli and Streptococcus pneumoniae across European countries and to identify factors that may shape resistance evolution in bacteria by modulating the intensity and outcomes of within-host competition.

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Code availability

C++ code for the individual-based model is available at https://github.com/nicholasdavies/tinyhost.

Data availability

All data used in this analysis are publicly available2,3.

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Acknowledgements

We thank M. Davies and A. Levy for assistance and S. Lehtinen, C. Colijn and M. Lipsitch for discussion. N.G.D., M.J. and K.E.A. were funded by the National Institute for Health Research Health Protection Research Unit in Immunisation at the London School of Hygiene and Tropical Medicine in partnership with Public Health England. The views expressed are those of the authors and not necessarily those of the NHS, National Institute for Health Research, Department of Health or Public Health England. For part of this work, S.F. was supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and Royal Society (grant number 208812/Z/17/Z).

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N.G.D., S.F., M.J. and K.E.A. conceived the study. N.G.D. performed the analyses. N.G.D. and K.E.A. drafted the manuscript, which was revised by all authors.

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Correspondence to Nicholas G. Davies.

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Davies, N.G., Flasche, S., Jit, M. et al. Within-host dynamics shape antibiotic resistance in commensal bacteria. Nat Ecol Evol 3, 440–449 (2019). https://doi.org/10.1038/s41559-018-0786-x

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