Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Rämistr. 100, RAE U, 8091, Zurich, Switzerland.
Eur J Clin Microbiol Infect Dis. 2018 Feb;37(2):289-292. doi: 10.1007/s10096-017-3130-5. Epub 2017 Nov 27.
Staphylococcus aureus endovascular infections retain a high morbidity and mortality despite antibiotics and supportive care. The destruction of endothelial cells (ECs) is a critical step in the pathogenesis of S. aureus endovascular infections. In order to better understand S. aureus-induced EC damage, we systematically screened a collection of two-component regulatory system mutants of methicillin-resistant S. aureus (MRSA) USA300 strain JE2 for damage induction in human umbilical vein ECs (HUVECs). This screen revealed that the two-component regulatory system ArlRS is required for maximum damage: arlRS inactivation leads to a > 70% reduction in damage. In a different genetic S. aureus background (RN6390, MSSA strain) arlRS inactivation had a smaller but also significant effect on EC damage. In both strains, the reduction in EC damage was accompanied by a significant reduction in internalization. In conclusion, we determined a novel role of ArlRS in S. aureus-induced EC damage, which will help to better understand the pathogenesis of S. aureus endovascular infection.
金黄色葡萄球菌（Staphylococcus aureus）血管内感染尽管采用抗生素和支持性治疗，但仍具有较高的发病率和死亡率。内皮细胞（endothelial cells，ECs）的破坏是金黄色葡萄球菌血管内感染发病机制中的一个关键步骤。为了更好地理解金黄色葡萄球菌引起的 EC 损伤，我们系统地筛选了耐甲氧西林金黄色葡萄球菌（methicillin-resistant S. aureus，MRSA）USA300 株 JE2 的二组分调控系统突变体库，以寻找其对人脐静脉内皮细胞（human umbilical vein ECs，HUVECs）的损伤诱导作用。该筛选揭示了二组分调控系统 ArlRS 对最大损伤的需要：arlRS 失活导致损伤减少>70%。在不同的遗传金黄色葡萄球菌背景（RN6390，MSSA 株）中，arlRS 失活对 EC 损伤也有较小但显著的影响。在这两种菌株中，EC 损伤的减少伴随着内化的显著减少。总之，我们确定了 ArlRS 在金黄色葡萄球菌诱导的 EC 损伤中的新作用，这将有助于更好地理解金黄色葡萄球菌血管内感染的发病机制。
