Streptococcus sanguinis induces neutrophil cell death by production of hydrogen peroxide.
Streptococcus sanguinis induces neutrophil cell death by production of hydrogen peroxide.
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DOI：
10.1371/journal.pone.0172223
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Kawabata S
中科院分区：
文献类型：
--
作者：
Sumioka R;Nakata M;Okahashi N;Li Y;Wada S;Yamaguchi M;Sumitomo T;Hayashi M;Kawabata S
链球菌是人类口腔中的优势细菌属，也是感染性心内膜炎的主要原因。血链球菌属于链球菌的缓症组，并通过SpxB（一种丙酮酸氧化酶）的作用产生过氧化氢（H2O2）。在这项研究中，我们调查了SpxB在S.血吸虫在人血液中的浓度以及细菌H2O2是否对人中性粒细胞表现出细胞毒性。人全血杀菌试验结果显示，S. sanguinis不利于其在血液中的存活。当S.将sanguinis菌株暴露于分离的中性粒细胞，spxB缺失显著降低了细菌存活率。此外，暴露于S.与暴露于spxB突变菌株的那些相比，血吸虫野生型菌株经历了细胞死亡，伴随染色质去凝聚和网状细胞外DNA的释放，反映了中性粒细胞细胞胞外陷阱（NET）的诱导。由于活性氧介导的NET诱导需要组蛋白中精氨酸残基的瓜氨酸化和随后的染色质去缩合，我们检测了受感染中性粒细胞中组蛋白的瓜氨酸水平。值得注意的是，与spxB突变株感染相比，瓜氨酸化组蛋白H3在野生型菌株感染的中性粒细胞中很容易检测到。此外，链球菌过氧化氢酶分解减少NET诱导。这些结果表明，S.血吸虫引起嗜中性粒细胞的细胞死亡和NET形成，从而潜在地影响血流中的细菌存活。
Streptococcus is the dominant bacterial genus in the human oral cavity and a leading cause of infective endocarditis. Streptococcus sanguinis belongs to the mitis group of streptococci and produces hydrogen peroxide (H2O2) by the action of SpxB, a pyruvate oxidase. In this study, we investigated the involvement of SpxB in survival of S. sanguinis in human blood and whether bacterial H2O2 exhibits cytotoxicity against human neutrophils. Results of a bactericidal test with human whole blood revealed that the spxB mutation in S. sanguinis is detrimental to its survival in blood. When S. sanguinis strains were exposed to isolated neutrophils, the bacterial survival rate was significantly decreased by spxB deletion. Furthermore, human neutrophils exposed to the S. sanguinis wild-type strain, in contrast to those exposed to an spxB mutant strain, underwent cell death with chromatin de-condensation and release of web-like extracellular DNA, reflecting induction of neutrophil extracellular traps (NETs). Since reactive oxygen species-mediated NET induction requires citrullination of arginine residues in histone proteins and subsequent chromatin de-condensation, we examined citrullination levels of histone in infected neutrophils. It is important to note that the citrullinated histone H3 was readily detected in neutrophils infected with the wild-type strain, as compared to infection with the spxB mutant strain. Moreover, decomposition of streptococcal H2O2 with catalase reduced NET induction. These results suggest that H2O2 produced by S. sanguinis provokes cell death of neutrophils and NET formation, thus potentially affecting bacterial survival in the bloodstream.