A Nuclease from Streptococcus mutans Facilitates Biofilm Dispersal and Escape from Killing by Neutrophil Extracellular Traps.
A Nuclease from Streptococcus mutans Facilitates Biofilm Dispersal and Escape from Killing by Neutrophil Extracellular Traps.
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来自变形链球菌的核酸酶促进生物膜分散并逃避中性粒细胞胞外陷阱的杀伤
DOI：
10.3389/fcimb.2017.00097
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发表时间：
2017
影响因子：
5.7
通讯作者：
Ling J
中科院分区：
文献类型：
--
作者：
Liu J;Sun L;Liu W;Guo L;Liu Z;Wei X;Ling J
变形链球菌是龋齿和偶尔感染性心内膜炎的主要病原，具有形成生物膜和将细胞分散到远端部位的能力，从而加剧和传播感染。在这项研究中，我们通过芯片分析确定了一种核酸酶（DeoC）作为变形链球菌生物膜分散调节因子。体外实验揭示了deoC缺失突变体的分散缺陷，纯化蛋白的功能研究表明了deoC的生物膜分散活性。中性粒细胞是一种关键的宿主反应因子，通过形成中性粒细胞胞外陷阱（NETs）来抑制细菌的传播，NETs由与抗菌肽相关的核DNA骨干组成。因此，我们假设分散的变形链球菌可能利用DeoC降解NETs并逃避免疫系统的杀伤。研究发现，变形链球菌在与中性粒细胞接触后诱导NET的形成，而NET的存在反过来又增强了变形链球菌deoC的表达。荧光显微镜检查显示，deoC缺失导致突变链球菌对NET的降解能力下降，对中性粒细胞杀伤的敏感性增强。本研究获得的数据表明DeoC在变形链球菌中的两个重要作用：通过介导生物膜扩散促进感染的传播，以及通过NET降解促进变形链球菌从中性粒细胞杀伤中逃脱。
Streptococcus mutans is the primary etiologic agent of dental caries and occasionally infective endocarditis, with the ability to form biofilms and disperse cells into distal sites to exacerbate and spread infection. In this study, we identified a nuclease (DeoC) as a S. mutans biofilm dispersal modulating factor through microarray analysis. In vitro assays revealed a dispersal defect of a deoC deletion mutant, and functional studies with purified protein were indicative of the biofilm dispersal activity of DeoC. Neutrophils are a key host response factor restraining bacterial spreading through the formation of neutrophil extracellular traps (NETs), which consist of a nuclear DNA backbone associated with antimicrobial peptides. Therefore, we hypothesized that the dispersed S. mutans might utilize DeoC to degrade NETs and escape killing by the immune system. It was found that S. mutans induced NET formation upon contact with neutrophils, while the presence of NETs in turn enhanced the deoC expression of S. mutans. Fluorescence microscopy inspection showed that deoC deletion resulted in a decreased NET degradation ability of S. mutans and enhanced susceptibility to neutrophil killing. Data obtained from this study assigned two important roles for DeoC in S. mutans: contributing to the spread of infection through mediating biofilm dispersal, and facilitating the escape of S. mutans from neutrophil killing through NET degradation.