Serotype-Dependent Effects on the Dynamics of Pneumococcal Colonization and Implications for Transmission.
Serotype-Dependent Effects on the Dynamics of Pneumococcal Colonization and Implications for Transmission.
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比较了荚膜转换突变体，以分析血清型如何影响肺炎链球菌（Spn）在定植和传播过程中的成功。在高度易感的幼鼠中测试了多种血清型的菌株，包括单独测试和竞争性测试。我们的研究结果表明，血清型的作用，除了遗传背景，在菌株的竞争成功，但这取决于接种后的时间。与自然携带的情况一样，使用胶囊转换菌株的血清型之间存在成功等级。收购后的第一个4小时内建立的血清型的长期优势，这表明一个独立的影响SPN诱导的主机响应。血清型优势的层次结构与体内清除率降低而非生长增加相关。竞争性试验错开挑战的时间表明，第一个菌株占主导地位的生态位保持其竞争优势，可能解释如何增加密度延迟早期清除可能导致依赖于基因型的成功。在群体感应机制的竞争操纵子调控的菌株内竞争（fratricide）的效应分子，需要早期的生态位优势。这表明一个赢家通吃的情况下，血清型是一个主要因素，在实现早期的生态位优势，这样，一旦一个菌株达到阈值密度，它能够排除竞争对手通过自相残杀。血清型也是传播动力学的一个重要决定因素，尽管转运到受体宿主取决于血清型的影响，而不是其对供体宿主中定植优势的贡献。
Capsule-switch mutants were compared to analyze how serotype affects the success of Streptococcus pneumoniae (Spn) during colonization and transmission. Strains of multiple serotypes were tested in highly susceptible infant mice, both singly and in competitive assays. Our findings demonstrated a role of serotype, apart from genetic background, in competitive success of strains, but this depended on timing postinoculation. As is the case for natural carriage, there was a hierarchy of success among serotypes using capsule-switch strains. The long-term dominance of a serotype was established within the first 4 h after acquisition, suggesting an effect independent of Spn-induced host responses. The hierarchy of serotype dominance correlated with decreased clearance rather than increased growth in vivo. Competitive assays staggering the timing of challenge showed that the first strain to dominate the niche sustained its competitive advantage, potentially explaining how increased density from delayed early clearance could result in serotype-dependent success. Effector molecules of intrastrain competition (fratricide), regulated by the competence operon in a quorum-sensing mechanism, were required for early niche dominance. This suggested a winner-takes-all scenario in which serotype is a major factor in achieving early niche dominance, such that once a strain reaches a threshold density it is able to exclude competitors through fratricide. Serotype was also an important determinant of transmission dynamics, although transit to a recipient host depended on effects of serotype different from its contribution to the dominance of colonization in the donor host.
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