The novel transcriptional regulator SA1804 Is involved in mediating the invasion and cytotoxicity of Staphylococcus aureus.
The novel transcriptional regulator SA1804 Is involved in mediating the invasion and cytotoxicity of Staphylococcus aureus.
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DOI：
10.3389/fmicb.2015.00174
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发表时间：
2015
影响因子：
5.2
通讯作者：
Ji Y
中科院分区：
文献类型：
--
作者：
Yang J;Liang X;Ji Y
双组分调控系统SaeRS控制重要毒力因子的表达，包括毒素和侵袭素，其有助于金黄色葡萄球菌的致病性。在此之前，我们进行了一项转录组学研究，以确定SaeRS调节子，发现SaeRS的失活显着增强了一种新的转录调节因子（SA 1804）的转录。这使我们怀疑SA 1804是否通过调节毒力因子的表达而参与细菌的致病性。为了解决这个问题，我们在USA 300社区获得的MRSA菌株923中创建了sa 1804、saeRS和sa 1804/saeRS双缺失突变体，并确定了它们对致病性的影响。sa 1804的缺失显著增加了细胞毒性并增强了细菌侵入上皮细胞（A549）的能力，而saeRS的缺失消除了细胞毒性并消除了细菌侵入上皮细胞的能力。此外，sa 1804和saeRS双缺失与saeRS无效突变表现出相似的表型。此外，我们使用qPCR和凝胶移位方法确定了SA 1804的调控机制。我们的数据表明，新的毒力阻遏物SA 1804是依赖于SaeRS的调节。本研究揭示了毒力因子的调控机制，为进一步阐明S.金黄色。
The two-component regulatory system, SaeRS, controls expression of important virulence factors, including toxins and invasins, which contribute to the pathogenicity of Staphylococcus aureus. Previously, we conducted a transcriptomics study for identification of SaeRS regulon and found that inactivation of SaeRS dramatically enhances the transcription of a novel transcriptional regulator (SA1804). This led us to question whether SA1804 is involved in bacterial pathogenicity by regulating the expression of virulence factors. To address this question, we created sa1804, saeRS, and sa1804/saeRS double deletion mutants in a USA300 community-acquired MRSA strain, 923, and determined their impact on the pathogenicity. The deletion of sa1804 dramatically increased the cytotoxicity and enhanced the capacity of bacteria to invade into the epithelial cells (A549), whereas the deletion of saeRS eliminated the cytotoxicity and abolished the bacterial ability to invade into the epithelial cells. Moreover, the double deletions of sa1804 and saeRS appeared a similar phenotype with the saeRS null mutation. Furthermore, we determined the regulatory mechanism of SA1804 using qPCR and gel-shift approaches. Our data indicate that the novel virulence repressor SA1804 is dependent on the regulation of SaeRS. This study sheds light on the regulatory mechanism of virulence factors and allows for us further elucidate the molecular pathogenesis of S. aureus.