Biphasic intracellular expression of Staphylococcus aureus virulence factors and evidence for Agr-mediated diffusion sensing
Biphasic intracellular expression of Staphylococcus aureus virulence factors and evidence for Agr-mediated diffusion sensing
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DOI：
10.1046/j.1365-2958.2003.03618.x
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发表时间：
2003-08-01
影响因子：
3.6
通讯作者：
Bayles, KW
中科院分区：
文献类型：
--
作者：
Shompole, S;Henon, KT;Bayles, KW
金黄色葡萄球菌侵入多种哺乳动物细胞，并从核内体逃逸到细胞质中繁殖。我们之前假设导致金黄色葡萄球菌从核内体逃逸的分子事件涉及Agr毒力因子调控系统。在本报告中，我们证明了细胞内Agr调控子激活的时间变化与膜活性毒素的表达相关。此外，即使少量葡萄球菌最初表达Agr也会导致内体膜的通透性，并最终在入侵后3小时逃逸到细胞质中。Agr下调后，第二个表达高峰与宿主细胞膜通透性增加一致。与亲本菌株相比，agr突变体无法逃逸到细胞质中，并且在入侵后5小时在完整的核内体中观察到。这些数据提供了葡萄球菌在入侵宿主细胞期间产生毒力因子是由agr依赖性过程介导的证据，该过程在扩散感应的背景下得到了最准确的描述。
Staphylococcus aureus invades a variety of mammalian cells and escapes from the endosome to multiply in the cytoplasm. We had previously hypothesized that the molecular events leading to escape of S. aureus from the endosome involved the Agr virulence factor regulatory system. In this report we demonstrate that temporal changes in intracellular activation of the Agr regulon correlates with expression of membrane active toxins. Also, the initial expression of Agr by even small numbers of staphylococci resulted in the permeabilization of the endosomal membrane and the eventual escape of bacteria into the cytoplasm by 3 h post invasion. After Agr downregulation, a second peak of expression coincided with increased permeability of the host cell membrane. In contrast to the parental strain, an Agr-mutant was unable to escape into the cytoplasm and was observed in intact endosomes as late as 5 h post invasion. These data provide evidence that staphylococcal virulence factor production during invasion of host cells is mediated by an Agr-dependent process that is most accurately described in the context of diffusion sensing.