Increased pathogenicity of pneumococcal serotype 1 is driven by rapid autolysis and release of pneumolysin
Increased pathogenicity of pneumococcal serotype 1 is driven by rapid autolysis and release of pneumolysin
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DOI：
10.1038/s41467-020-15751-6
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发表时间：
2020-04-20
影响因子：
16.6
通讯作者：
Kadioglu，Aras
中科院分区：
文献类型：
--
作者：
Jacques，Laura C.;Panagiotou，Stavros;Kadioglu，Aras
肺炎链球菌1型是撒哈拉以南非洲地区侵袭性肺炎球菌疾病的主要原因，但其侵袭性增加背后的机制尚不清楚。在这里，我们使用肺部感染的小鼠模型，以确定与严重菌血症性肺炎血清1型（ST 217）感染的毒力因子。我们使用BALB/c小鼠，当感染其他血清型时，它们对肺炎球菌肺炎具有高度抵抗力。然而，当BALB/c小鼠鼻内感染ST 217时，我们在24小时内观察到100%的死亡率和高水平的菌血症。血清型1产生大量肺炎球菌溶血素，其由于高水平的细菌自溶而快速释放。这导致大量细胞毒性和细胞间紧密连接的破坏，从而为细菌从呼吸道快速传播到血液中提供了途径。因此，我们的研究结果提供了一个解释血清1型的侵袭性增加。
Streptococcus pneumoniaeserotype 1 is the predominant cause of invasive pneumococcal disease in sub-Saharan Africa, but the mechanism behind its increased invasiveness is not well understood. Here, we use mouse models of lung infection to identify virulence factors associated with severe bacteraemic pneumonia during serotype-1 (ST217) infection. We use BALB/c mice, which are highly resistant to pneumococcal pneumonia when infected with other serotypes. However, we observe 100% mortality and high levels of bacteraemia within 24 hours when BALB/c mice are intranasally infected with ST217. Serotype 1 produces large quantities of pneumolysin, which is rapidly released due to high levels of bacterial autolysis. This leads to substantial levels of cellular cytotoxicity and breakdown of tight junctions between cells, allowing a route for rapid bacterial dissemination from the respiratory tract into the blood. Thus, our results offer an explanation for the increased invasiveness of serotype 1.