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Staphylococcus aureus Agr and Sar Global Regulators Influence Internalization and Induction of Apoptosis

机译:金黄色葡萄球菌Agr和Sar全球调节剂影响细胞凋亡的内在化和诱导

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Staphylococcus aureus was recently shown to be internalized by and to induce apoptosis in a bovine mammary epithelial cell line, suggesting that these processes could be involved in staphylococcal pathogenesis or persistence. To examine the role of virulence factor regulators during internalization, mutantagr and sar strains of S. aureuswere analyzed for their abilities to enter and induce apoptosis in epithelial cells. Like a previously characterized bovine mastitis isolate, the standard laboratory strain, RN6390 (wild type), entered the epithelial cells and subsequently induced apoptosis. In contrast, the mutant strains RN6911 (agr), ALC136 (sar), and ALC135 (agr sar) were internalized by the cultured cells at levels reproducibly greater than that for RN6390 but failed to induce apoptosis. The internalization of S. aureus was affected by growth phase, suggesting a role foragr-regulated surface proteins in this process. Furthermore, the ability to induce apoptosis required metabolically active intracellular bacteria. These data indicate that the ability ofS. aureus to enter mammalian cells and induce apoptosis is dependent on factors regulated by Agr and Sar. Since transcriptional control by these global regulators is mediated by quorum-sensing and environmental factors, staphylococci may have the potential to induce several alternative effects on cells from an intracellular environment. A model for the function of the agr locus in the context of internalization, intracellular persistence, and dissemination is proposed.
机译:最近发现金黄色葡萄球菌被牛乳腺上皮细胞系内化并诱导其凋亡,表明这些过程可能与葡萄球菌的发病机理或持久性有关。为了检查毒力因子调节剂在内部化过程中的作用,突变体是 S的 agr sar 菌株。分析了金黄色葡萄球菌上皮细胞进入和诱导凋亡的能力。像以前鉴定的牛乳腺炎分离株一样,标准实验室菌株RN6390(野生型)进入上皮细胞,随后诱导凋亡。相反,突变株RN6911( agr ),ALC136( sar )和ALC135( agr sar )被培养的细胞在RN6390的水平可再现地更高,但未能诱导凋亡。 S的内部化。金黄色葡萄球菌受生长阶段的影响,提示在此过程中 agr 调控的表面蛋白的作用。此外,诱导细胞凋亡的能力需要具有代谢活性的细胞内细菌。这些数据表明 S的能力。金黄色葡萄球菌进入哺乳动物细胞并诱导细胞凋亡取决于Agr和Sar调控的因子。由于这些全局调节因子的转录控制是由群体感应和环境因素介导的,因此葡萄球菌可能具有诱导细胞内环境对细胞产生多种替代作用的潜力。提出了一个在内部化,细胞内持久性和传播背景下 agr 基因座功能的模型。

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