The AirSR two-component system contributes to Staphylococcus aureus survival in human blood and transcriptionally regulates sspABC operon.

The AirSR two-component system contributes to Staphylococcus aureus survival in human blood and transcriptionally regulates sspABC operon.
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DOI:
10.3389/fmicb.2015.00682
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发表时间:
2015
影响因子:
5.2
通讯作者:
Ji Y
Ji Y
中科院分区:
生物学2区
文献类型:
--
作者:
Hall JW;Yang J;Guo H;Ji Y

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迄今为止,由AirSR TCS鉴定和转录调控的基因已参与葡萄球菌细胞的能量产生和细胞稳态。人们普遍认为,细胞代谢状态影响金黄色葡萄球菌毒力因子的表达。因此,我们通过反义RNA干扰技术、诱导型过表达系统和基因缺失实验来确定AirSR TCS是否与金黄色葡萄球菌的发病机制有关。通过反义RNA表达或基因缺失导致AirSR的缺失,可显著降低细菌在人血液中的存活率。相反,过表达AirR可显著促进金黄色葡萄球菌在血液中的存活。AirR促进毒力因子的分泌,抑制基于调理素的吞噬作用。这种增强的存活率部分与sspABC操纵子的转录调控有关,该操纵子编码V8蛋白酶(SspA)、葡萄球菌蛋白酶B (SspB)和葡萄球菌蛋白酶B (SspC)。SspA和SspB是已知的毒力因子,其蛋白水解消化调理素并抑制专业吞噬细胞对金黄色葡萄球菌的杀伤。这是将AirSR TCS与金黄色葡萄球菌发病机制联系起来的第一个证据。
To date, genes identified and transcriptionally regulated by the AirSR TCS have been involved in energy production and cellular homeostasis of the staphylococcal cell. It is well accepted that the state of cellular metabolism impacts the expression of virulence factors in Staphylococcus aureus. For this reason, we conducted experiments to determine if the AirSR TCS contributes to the pathogenesis of S. aureus using an antisense RNA interference technology, an inducible overexpression system, and gene deletions. Depletion of AirSR by antisense RNA expression or deletion of the genes, results in significant decrease in bacterial survival in human blood. Conversely, overexpression of AirR significantly promotes survival of S. aureus in blood. AirR promotes the secretion of virulence factors that inhibits opsonin-based phagocytosis. This enhanced survival is partially linked to the transcriptional regulation of the sspABC operon, encoding V8 protease (SspA), staphopain B (SspB) and staphostatin B (SspC). SspA and SspB are known virulence factors which proteolytically digest opsonins and inhibit killing of S. aureus by professional phagocytes. This is the first evidence linking the AirSR TCS to pathogenesis of S. aureus.
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