The two-component system VicRK regulates functions associated with Streptococcus mutans resistance to complement immunity.
The two-component system VicRK regulates functions associated with Streptococcus mutans resistance to complement immunity.
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DOI：
10.1111/omi.12183
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发表时间：
2017-10
影响因子：
3.7
通讯作者：
Mattos-Graner RO
中科院分区：
文献类型：
--
作者：
Alves LA;Harth-Chu EN;Palma TH;Stipp RN;Mariano FS;Höfling JF;Abranches J;Mattos-Graner RO
变形链球菌是一种龋齿病原体，在到达血液后可促进全身感染。本文报道了S.变形杆菌调节蔗糖衍生的胞外多糖（EPS）的合成和相互作用，这是与口服和全身毒力相关的过程。在这项研究中，我们研究了VicRKSm影响S.变形菌对血液介导的免疫的易感性。与亲本菌株UA 159相比，vicKSm等基因突变株（UAvic）对补体C3 b沉积的敏感性降低，与血清IgG的结合降低，并且以蔗糖非依赖性方式由PMN介导的C3 b/IgG调理吞噬作用的频率降低（p<0.05）。比较UA 159和UAvic中基因表达的RT-qPCR分析显示，在血清存在下，编码补体的推定肽酶（pepO和Smu.399）的基因在UAvic中上调，尽管编码胞壁蛋白水解酶（SmaA和Smu.2146c）或参与细菌与宿主组分相互作用的代谢/表面蛋白（烯醇化酶、GAPDH）的基因主要以血清非依赖性方式受到影响。在vicKSm下游基因（smaA、smu.2146c、lysM、atlA、pepO、smu.399）中，只有pepO和smu.399与UAvic表型相关; UA 159中这两个基因的缺失显著增强C3 b沉积和调理吞噬作用水平（p<0.05）。此外，与PepO直向同源物的纤连蛋白结合功能一致，UAvic显示与纤连蛋白的结合增加。对调理吞噬作用的敏感性降低不足以增强UAvic在血液中的离体持久性，这与该突变体在有限营养条件下的生长缺陷有关。结果表明，S.变形链球菌利用通过受VicRKSm控制的肽酶的补体逃避机制。
Streptococcus mutans, a dental caries pathogen, can promote systemic infections upon reaching the bloodstream. The two-component system (TCS) VicRKSm of S. mutans regulates the synthesis of and interaction with sucrose-derived exopolysaccharides (EPS), processes associated with oral and systemic virulence. In this study, we investigated the mechanisms by which VicRKSm affects S. mutans susceptibility to blood-mediated immunity. Compared to parent strain UA159, the vicKSm isogenic mutant (UAvic) showed reduced susceptibility to deposition of C3b of complement, low binding to serum IgG, and low frequency of C3b/IgG-mediated opsonophagocytosis by PMN in a sucrose-independent way (p<0.05). RT-qPCR analysis comparing gene expression in UA159 and UAvic revealed that genes encoding putative peptidases of the complement (pepO and smu.399) were up-regulated in UAvic in the presence of serum, although genes encoding murein hydrolases (SmaA and Smu.2146c) or metabolic/surface proteins involved in bacterial interactions with host components (enolase, GAPDH) were mostly affected in a serum-independent way. Among vicKSm-downstream genes (smaA, smu.2146c, lysM, atlA, pepO, smu.399), only pepO and smu.399 were associated with UAvic phenotypes; deletion of both genes in UA159 significantly enhanced levels of C3b deposition and opsonophagocytosis (p<0.05). Moreover, consistent with the fibronectin-binding function of PepO orthologues, UAvic showed increased binding to fibronectin. Reduced susceptibility to opsonophagocytosis was insufficient to enhance ex vivo persistence of UAvic in blood, which was associated with growth defects of this mutant under limited nutrient conditions. Our findings revealed that S. mutans employs mechanisms of complement evasion through peptidases which are controlled by VicRKSm.
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