What is the mechanism for persistent coexistence of drug-susceptible and drug-resistant strains of Streptococcus pneumoniae?
What is the mechanism for persistent coexistence of drug-susceptible and drug-resistant strains of Streptococcus pneumoniae?
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肺炎链球菌的持续共存和抗药性菌株的持续共存的机制是什么？
DOI：
10.1098/rsif.2009.0400
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发表时间：
2010-06-06
影响因子：
3.9
通讯作者：
Lipsitch, Marc
中科院分区：
文献类型：
--
作者：
Colijn, Caroline;Cohen, Ted;Fraser, Christophe;Hanage, William;Goldstein, Edward;Givon-Lavi, Noga;Dagan, Ron;Lipsitch, Marc
许多病原体抗菌素耐药性的上升对传染病的治疗和控制提出了重大挑战。此外，尽管抗菌药物使用持续（甚至不断增加）的选择性压力，但耐药菌株的流行率已大幅上升，但尚未取代药物敏感菌株，这对研究传染病动态的人来说是一个重要问题。虽然简单的竞争模型预测会排除一种菌株，而选择“更适合”或具有更高繁殖数的菌株，但我们认为，就肺炎链球菌而言，药物敏感菌株和耐药菌株一直共存，两者的流行率都未接近 100%。我们之前曾提出，寻求理解共存起源的模型不应包含“免费”构建稳定共存的隐含机制。在这里，我们构建了一系列此类“结构中性”模型，其中结合了细菌传播和宿主异质性的各种特征，这些特征已被提出作为可能促进共存的机制。我们询问共存在多大程度上是每个国家的典型结果。我们发现，虽然我们考虑的每个模型中都可能存在共存，但这种情况相对罕见，但有两个例外：（i）允许敏感菌株和耐药菌株同时双重传播，使共存成为一种典型的结果，（ii）将每个菌株建模为与自身的竞争比与其他菌株的竞争更强烈，即自身免疫大于交叉免疫。我们的结论是，虽然治疗和接触异质性可以在一定程度上促进共存，但菌株之间的宿主内相互作用，特别是共感染、多重感染和免疫之间的相互作用，在耐药病原体的长期种群动态中发挥着至关重要的作用。
The rise of antimicrobial resistance in many pathogens presents a major challenge to the treatment and control of infectious diseases. Furthermore, the observation that drug-resistant strains have risen to substantial prevalence but have not replaced drug-susceptible strains despite continuing (and even growing) selective pressure by antimicrobial use presents an important problem for those who study the dynamics of infectious diseases. While simple competition models predict the exclusion of one strain in favour of whichever is ‘fitter’, or has a higher reproduction number, we argue that in the case of Streptococcus pneumoniae there has been persistent coexistence of drug-sensitive and drug-resistant strains, with neither approaching 100 per cent prevalence. We have previously proposed that models seeking to understand the origins of coexistence should not incorporate implicit mechanisms that build in stable coexistence ‘for free’. Here, we construct a series of such ‘structurally neutral’ models that incorporate various features of bacterial spread and host heterogeneity that have been proposed as mechanisms that may promote coexistence. We ask to what extent coexistence is a typical outcome in each. We find that while coexistence is possible in each of the models we consider, it is relatively rare, with two exceptions: (i) allowing simultaneous dual transmission of sensitive and resistant strains lets coexistence become a typical outcome, as does (ii) modelling each strain as competing more strongly with itself than with the other strain, i.e. self-immunity greater than cross-immunity. We conclude that while treatment and contact heterogeneity can promote coexistence to some extent, the in-host interactions between strains, particularly the interplay between coinfection, multiple infection and immunity, play a crucial role in the long-term population dynamics of pathogens with drug resistance.
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影响因子：
5.2
作者：
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通讯作者：
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