Pyruvate oxidase of Streptococcus pneumoniae contributes to pneumolysin release
Pyruvate oxidase of Streptococcus pneumoniae contributes to pneumolysin release
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DOI：
10.1186/s12866-016-0881-6
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发表时间：
2016-11-09
期刊：
影响因子：
4.2
通讯作者：
Thornton, Justin A.
中科院分区：
文献类型：
--
作者：
Bryant, Joseph C.;Dabbs, Ridge C.;Thornton, Justin A.
背景：肺炎链球菌是引起社区获得性肺炎和急性中耳炎的主要原因之一。肺炎链球菌毒力的某些方面依赖于蛋白毒素溶肺素（PLY）的表达和释放，以及产生过氧化物酶丙酮酸氧化酶（SpxB）的活性。我们研究了这两种蛋白可能的协同作用，并发现在固定期生长之前，SpxB的表达增强了PLY的释放。结果：缺乏spxB基因的突变体在PLY释放方面存在缺陷，而spxB基因的补充可以恢复PLY的释放。无菌过滤上清液对上皮细胞和红细胞的细胞毒性作用证明了这一点。此外，过氧化氢的产生似乎有助于PLY释放的机制，因为在一组临床分离株中发现了过氧化氢产生和PLY释放之间的显著相关性。在一些菌株中，外源添加H2O2不能诱导PLY释放，而过氧化氢酶的添加阻止了PLY的释放，这表明过氧化物可能在细胞内或以菌株依赖的方式发挥作用。SpxB的表达不会引发细菌细胞死亡或lyta依赖性自溶，但会使细胞倾向于脱氧胆酸溶解。结论：我们发现了spxB表达与PLY释放之间的新联系。这些发现将PLY毒素的释放与氧气可用性和肺炎球菌代谢联系起来。
Background: Streptococcus pneumoniae is one of the leading causes of community acquired pneumonia and acute otitis media. Certain aspects of S. pneumoniae's virulence are dependent upon expression and release of the protein toxin pneumolysin (PLY) and upon the activity of the peroxide-producing enzyme, pyruvate oxidase (SpxB). We investigated the possible synergy of these two proteins and identified that release of PLY is enhanced by expression of SpxB prior to stationary phase growth.Results: Mutants lacking the spxB gene were defective in PLY release and complementation of spxB restored PLY release. This was demonstrated by cytotoxic effects of sterile filtered supernatants upon epithelial cells and red blood cells. Additionally, peroxide production appeared to contribute to the mechanism of PLY release since a significant correlation was found between peroxide production and PLY release among a panel of clinical isolates. Exogenous addition of H2O2 failed to induce PLY release and catalase supplementation prevented PLY release in some strains, indicating peroxide may exert its effect intracellularly or in a strain-dependent manner. SpxB expression did not trigger bacterial cell death or LytA-dependent autolysis, but did predispose cells to deoxycholate lysis.Conclusions: Here we demonstrate a novel link between spxB expression and PLY release. These findings link liberation of PLY toxin to oxygen availability and pneumococcal metabolism.