Evolution of antibiotic resistance is linked to any genetic mechanism affecting bacterial duration of carriage
Evolution of antibiotic resistance is linked to any genetic mechanism affecting bacterial duration of carriage
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DOI：
10.1073/pnas.1617849114
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发表时间：
2017-01-31
影响因子：
11.1
通讯作者：
Fraser, Christophe
中科院分区：
文献类型：
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作者：
Lehtinen, Sonja;Blanquart, Francois;Fraser, Christophe
了解抗生素消费的变化如何影响细菌病原体中抗生素耐药性的流行对公共卫生至关重要。在一些细菌物种中，包括肺炎链球菌，尽管抗生素的选择压力很长，但耐药性的流行仍然相对稳定。允许抗生素敏感菌株和耐药菌株稳健共存的进化过程尚未完全了解。虽然等位基因多样性可以通过直接平衡选择保持在一个基因座上，但没有证据表明这种选择在抗性的情况下起作用。在这项工作中，我们提出了一种维持抗性位点共存的机制：与处于平衡选择下并调节抗性适应性效应的第二个位点连锁。我们表明，持续时间的运输起着这样的作用，与长时间的运输增加健身优势从阻力。因此，我们预测耐药性在携带时间长的菌株中将更常见，保持携带时间多样性的机制也将保持抗生素耐药性的多样性。我们在S. pneumoniae，发现血清型携带的持续时间确实与该血清型的耐药率呈正相关。这些结果表明，异质性的持续时间的运输是一个敏感和耐药菌株的共存的部分解释，决定细菌的持续时间的因素也将影响耐药的流行。
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.