Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Cobey S

PROVIDER: S-EPMC5582124 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Cobey Sarah S Baskerville Edward B EB Colijn Caroline C Hanage William W Fraser Christophe C Lipsitch Marc M

Journal of the Royal Society, Interface 20170801 133

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, <i>Streptococcus pneumoniae</i> has demonstrated persistent coexistence of drug-sensitive and drug-resistant strains. Theoretically, this outcome is unlikely. We modelled the dynamics of competing strains of <i>S. pneumoniae</i> to investigate the impact of transmission dynamics and treatment-ind ...[more]

PMID: 28835542

Similar Datasets

Project description:Arbutus unedo L. is an evergreen shrub with a circum-Mediterranean distribution that also reaches the Eurosiberian region in northern Iberia, Atlantic France, and a disjunct population in southern Ireland. Due to the variety of climatic conditions across its distribution range, the populations of A. unedo were expected to display local adaptation. Conversely, common garden experiments revealed that diverse genotypes from a range of provenances produce similar phenotypes through adaptive plasticity, suggesting the action of stabilizing selection across its climatically heterogeneous range. Nonetheless, since a uniform response might also result from extensive gene flow, we have inferred the population structure of A. unedo and assessed whether its extended and largely one-dimensional range influences gene flow with the help of AFLP genotypes for 491 individuals from 19 populations covering the whole range of the species. As we had anticipated, gene flow is restricted in A. unedo, providing further support to the hypothesis that stabilizing selection is the most likely explanation for the homogeneous phenotypes along the range. The Euro-Siberian populations were not particularly isolated from the Mediterranean. Instead, there was a distinct genetic divide between the populations around the Mediterranean Sea and those sampled along Atlantic coasts from northern Africa up to Ireland. This genetic structure suggests the action of historic rather than biogeographic factors as it seems consistent with a scenario of independent glacial refugia in the Atlantic and Mediterranean portions of the range of A. unedo. Genetic exchange was likewise restricted within each set of populations. Nevertheless, isolation-by-distance (IBD) was stronger, and F ST increased faster with distance, along the Atlantic, suggesting that gene flow might be larger among Mediterranean populations. Genetic diversity was significantly lower in NW Iberia and Ireland than in other populations whereas Ireland was more closely related to populations in NW Iberia than to a population in Atlantic France, suggesting a postglacial stepping-stone colonization of the Atlantic coast. Altogether, our results show that stabilizing selection is able to homogenize the phenotypic response even when population structure is strong, gene flow is constrained, and the phylogeographic past is complex.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets