Bacterial Factors Required for Transmission of Streptococcus pneumoniae in Mammalian Hosts.
Bacterial Factors Required for Transmission of Streptococcus pneumoniae in Mammalian Hosts.
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DOI：
10.1016/j.chom.2019.04.012
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发表时间：
2019-06
影响因子：
30.3
通讯作者：
Hannah M. Rowe;E. Karlsson;H. Echlin;Ti‐Cheng Chang;Lei Wang;T. van Opijnen;S. Pounds;S. Schultz‐Cherry;J. Rosch
中科院分区：
文献类型：
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作者：
Hannah M. Rowe;E. Karlsson;H. Echlin;Ti‐Cheng Chang;Lei Wang;T. van Opijnen;S. Pounds;S. Schultz‐Cherry;J. Rosch
肺炎链球菌成功传播和定居新的人类宿主的能力是肺炎球菌群体生物学的一个关键方面，也是侵袭性疾病的先决条件。然而，这一过程背后的细菌机制在很大程度上仍然未知。为了确定传播所需的细菌因素，我们在雪貂传播模型中用肺炎球菌菌株的转座子测序（Tn-seq）文库进行了高通量遗传筛选。代谢和转录调控的关键参与者被确定为有效的细菌传播所需的。在小鼠模型中，靶向缺失推定的C3降解蛋白酶CppA、铁转运蛋白PiaA或感受态调节性组氨酸激酶ComD显著降低了传递性，进一步验证了筛选。母体接种重组表面暴露的PiaA和CppA单独或组合阻断了后代的传播，比胶囊疫苗更有效。这些数据强调了将肺炎球菌传播作为消除人群中侵袭性疾病的一种手段的可能性。
The capacity ofStreptococcus pneumoniaeto successfully transmit and colonize new human hosts is a critical aspect of pneumococcal population biology and a prerequisite for invasive disease. However, the bacterial mechanisms underlying this process remain largely unknown. To identify bacterial factors required for transmission, we conducted a high-throughput genetic screen with a transposon sequencing (Tn-seq) library of a pneumococcal strain in a ferret transmission model. Key players in both metabolism and transcriptional regulation were identified as required for efficient bacterial transmission. Targeted deletion of the putative C3-degrading protease CppA, iron transporter PiaA, or competence regulatory histidine kinase ComD significantly decreased transmissibility in a mouse model, further validating the screen. Maternal vaccination with recombinant surface-exposed PiaA and CppA alone or in combination blocked transmission in offspring and were more effective than capsule-based vaccines. These data underscore the possibility of targeting pneumococcal transmission as a means of eliminating invasive disease in the population.