期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2017
卷号：114
期号：5
页码：1075-1080
DOI：10.1073/pnas.1617849114
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceThe relationship between a populations antibiotic consumption and the frequency of antibiotic resistance among bacteria colonizing that population is not fully understood. Antibiotic resistant and sensitive strains compete for available hosts--we would therefore expect the fitter strain to dominate. Instead, we observe stable coexistence of both strains. In this work, we propose an explanation for this coexistence by showing the fitness advantage of resistance depends on a bacterial strains duration of carriage. This finding ties the evolution of resistance to any genetic mechanism affecting duration of carriage. These insights could allow more accurate prediction of future resistance levels and play a role in informing strategies to prevent the spread of resistance. Understanding how changes in antibiotic consumption affect the prevalence of antibiotic resistance in bacterial pathogens is important for public health. In a number of bacterial species, including Streptococcus pneumoniae, the prevalence of resistance has remained relatively stable despite prolonged selection pressure from antibiotics. The evolutionary processes allowing the robust coexistence of antibiotic sensitive and resistant strains are not fully understood. While allelic diversity can be maintained at a locus by direct balancing selection, there is no evidence for such selection acting in the case of resistance. In this work, we propose a mechanism for maintaining coexistence at the resistance locus: linkage to a second locus that is under balancing selection and that modulates the fitness effect of resistance. We show that duration of carriage plays such a role, with long duration of carriage increasing the fitness advantage gained from resistance. We therefore predict that resistance will be more common in strains with a long duration of carriage and that mechanisms maintaining diversity in duration of carriage will also maintain diversity in antibiotic resistance. We test these predictions in S. pneumoniae and find that the duration of carriage of a serotype is indeed positively correlated with the prevalence of resistance in that serotype. These findings suggest heterogeneity in duration of carriage is a partial explanation for the coexistence of sensitive and resistant strains and that factors determining bacterial duration of carriage will also affect the prevalence of resistance.
