A Staphylococcus aureus regulatory system that responds to host heme and modulates virulence
A Staphylococcus aureus regulatory system that responds to host heme and modulates virulence
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DOI：
10.1016/j.chom.2007.03.001
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发表时间：
2007-04-01
影响因子：
30.3
通讯作者：
Skaar, Eric P.
中科院分区：
文献类型：
--
作者：
Torres, Victor J.;Stauff, Devin L.;Skaar, Eric P.
金黄色葡萄球菌是一种造成巨大发病率和死亡率的细菌，它作为无害的共生菌存在于大约 25% 的人类体内。识别感染后激活的分子机制对于了解葡萄球菌发病机制至关重要。我们描述了血红素传感器系统（HssRS），它响应血红素暴露并激活血红素调节转运蛋白（HrtAB）的表达。 Hss 或 Hrt 系统的失活会导致脊椎动物感染模型中毒力增加，这是一种与先天免疫反应受抑制相关的表型。我们认为 Hss 和 Hrt 的协调活性使金黄色葡萄球菌能够感知内部宿主组织，从而调节毒力以避免宿主组织过度损伤。此外，基因组分析已经在炭疽芽孢杆菌、单核细胞增生李斯特菌和粪肠球菌中鉴定出直向同源的 Hss 和 Hrt 系统，表明革兰氏阳性病原体通过该系统将血红素感知为内部宿主组织的分子标记并调节毒力。
Staphylococcus aureus, a bacterium responsible for tremendous morbidity and mortality, exists as a harmless commensal in approximately 25% of humans. Identifying the molecular machinery activated upon infection is central to understanding staphylococcal pathogenesis. We describe the heme sensor system (HssRS) that responds to heme exposure and activates expression of the heme-regulated transporter (HrtAB). Inactivation of the Hss or Hrt systems leads to increased virulence in a vertebrate infection model, a phenotype that is associated with an inhibited innate immune response. We suggest that the coordinated activity of Hss and Hrt allows S. aureus to sense internal host tissues, resulting in tempered virulence to avoid excessive host tissue damage. Further, genomic analyses have identified orthologous Hss and Hrt systems in Bacillus anthracis, Listeria monocytogenes, and Enterococcus faecalis, suggesting a conserved regulatory system by which Gram-positive pathogens sense heme as a molecular marker of internal host tissue and modulate virulence.