Host population structure and treatment frequency maintain balancing selection on drug resistance.
Host population structure and treatment frequency maintain balancing selection on drug resistance.
复制标题
DOI：
10.1098/rsif.2017.0295
复制
发表时间：
2017-08
期刊：
影响因子：
--
通讯作者：
Lipsitch M
中科院分区：
文献类型：
--
作者：
Cobey S;Baskerville EB;Colijn C;Hanage W;Fraser C;Lipsitch M
众所周知，抗微生物药物选择耐药性，但解释病原体和人群特异性耐药模式的变化仍然是一个悬而未决的问题。肺炎链球菌与其他常见细菌一样，耐药菌株和敏感菌株并存。从理论上讲，这种结果不太可能。我们模拟了S. pneumoniae研究传播动力学和治疗诱导的选择性压力对稳定共存概率的影响。我们发现，竞争的结果是非常敏感的结构，在主机人口，虽然共存可能会出现从年龄不等的抗生素使用率与年龄的传播模型。此外，我们发现，抗生素的选择性压力并不是来自抗生素的使用率本身，而是来自治疗的频率：频繁的抗生素治疗不成比例地影响敏感菌株的适应性。同样的现象也解释了为什么携带时间较长的血清型往往更耐药。这些动态可能适用于其他潜在的致病性微生物，并突出了模型中经常忽略的种群结构如何产生巨大影响。
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.
登录
查看更多内容
影响因子：
120.7
作者：
Grijalva, Carlos G.;Nuorti, J. Pekka;Griffin, Marie R.
通讯作者：
Griffin, Marie R.
影响因子：
11.8
作者：
Goossens, Herman;Ferech, Matus;Stephens, Peter
通讯作者：
Stephens, Peter
影响因子：
6.4
作者：
GRAY, BM;CONVERSE, GM;DILLON, HC
通讯作者：
DILLON, HC
DOI：
10.1073/pnas.1617849114
发表时间：
2017-01-31
影响因子：
11.1
作者：
Lehtinen, Sonja;Blanquart, Francois;Fraser, Christophe
通讯作者：
Fraser, Christophe
影响因子：
3.8
作者：
Lipsitch, Marc;Colijn, Caroline;Cohen, Ted;Hanage, William P.;Fraser, Christophe
通讯作者：
Fraser, Christophe