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Host population structure and treatment frequency maintain balancing selection on drug resistance

It is a truism that antimicrobial drugs select for resistance, but explaining pathogen- and population-specific variation in patterns of resistance remains an open problem. Like other common commensals, Streptococcus pneumoniae has demonstrated persistent coexistence of drug-sensitive and drug-resis...

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Autores principales: Cobey, Sarah, Baskerville, Edward B., Colijn, Caroline, Hanage, William, Fraser, Christophe, Lipsitch, Marc
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5582124/
https://www.ncbi.nlm.nih.gov/pubmed/28835542
http://dx.doi.org/10.1098/rsif.2017.0295
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author Cobey, Sarah
Baskerville, Edward B.
Colijn, Caroline
Hanage, William
Fraser, Christophe
Lipsitch, Marc
author_facet Cobey, Sarah
Baskerville, Edward B.
Colijn, Caroline
Hanage, William
Fraser, Christophe
Lipsitch, Marc
author_sort Cobey, Sarah
collection PubMed
description It is a truism that antimicrobial drugs select for resistance, but explaining pathogen- and population-specific variation in patterns of resistance remains an open problem. Like other common commensals, Streptococcus pneumoniae has demonstrated persistent coexistence of drug-sensitive and drug-resistant strains. Theoretically, this outcome is unlikely. We modelled the dynamics of competing strains of S. pneumoniae to investigate the impact of transmission dynamics and treatment-induced selective pressures on the probability of stable coexistence. We find that the outcome of competition is extremely sensitive to structure in the host population, although coexistence can arise from age-assortative transmission models with age-varying rates of antibiotic use. Moreover, we find that the selective pressure from antibiotics arises not so much from the rate of antibiotic use per se but from the frequency of treatment: frequent antibiotic therapy disproportionately impacts the fitness of sensitive strains. This same phenomenon explains why serotypes with longer durations of carriage tend to be more resistant. These dynamics may apply to other potentially pathogenic, microbial commensals and highlight how population structure, which is often omitted from models, can have a large impact.
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spelling pubmed-55821242017-09-12 Host population structure and treatment frequency maintain balancing selection on drug resistance Cobey, Sarah Baskerville, Edward B. Colijn, Caroline Hanage, William Fraser, Christophe Lipsitch, Marc J R Soc Interface Life Sciences–Mathematics interface It is a truism that antimicrobial drugs select for resistance, but explaining pathogen- and population-specific variation in patterns of resistance remains an open problem. Like other common commensals, Streptococcus pneumoniae has demonstrated persistent coexistence of drug-sensitive and drug-resistant strains. Theoretically, this outcome is unlikely. We modelled the dynamics of competing strains of S. pneumoniae to investigate the impact of transmission dynamics and treatment-induced selective pressures on the probability of stable coexistence. We find that the outcome of competition is extremely sensitive to structure in the host population, although coexistence can arise from age-assortative transmission models with age-varying rates of antibiotic use. Moreover, we find that the selective pressure from antibiotics arises not so much from the rate of antibiotic use per se but from the frequency of treatment: frequent antibiotic therapy disproportionately impacts the fitness of sensitive strains. This same phenomenon explains why serotypes with longer durations of carriage tend to be more resistant. These dynamics may apply to other potentially pathogenic, microbial commensals and highlight how population structure, which is often omitted from models, can have a large impact. The Royal Society 2017-08 2017-08-23 /pmc/articles/PMC5582124/ /pubmed/28835542 http://dx.doi.org/10.1098/rsif.2017.0295 Text en © 2017 The Authors. http://creativecommons.org/licenses/by/4.0/ Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.
spellingShingle Life Sciences–Mathematics interface
Cobey, Sarah
Baskerville, Edward B.
Colijn, Caroline
Hanage, William
Fraser, Christophe
Lipsitch, Marc
Host population structure and treatment frequency maintain balancing selection on drug resistance
title Host population structure and treatment frequency maintain balancing selection on drug resistance
title_full Host population structure and treatment frequency maintain balancing selection on drug resistance
title_fullStr Host population structure and treatment frequency maintain balancing selection on drug resistance
title_full_unstemmed Host population structure and treatment frequency maintain balancing selection on drug resistance
title_short Host population structure and treatment frequency maintain balancing selection on drug resistance
title_sort host population structure and treatment frequency maintain balancing selection on drug resistance
topic Life Sciences–Mathematics interface
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5582124/
https://www.ncbi.nlm.nih.gov/pubmed/28835542
http://dx.doi.org/10.1098/rsif.2017.0295
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