RT Journal Article
SR Electronic
T1 Host population structure and treatment frequency maintain balancing selection on drug resistance
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 128967
DO 10.1101/128967
A1 Sarah Cobey
A1 Edward B. Baskerville
A1 Caroline Colijn
A1 William Hanage
A1 Christophe Fraser
A1 Marc Lipsitch
YR 2017
UL http://biorxiv.org/content/early/2017/04/20/128967.abstract
AB 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 modeled 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.