Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
Microb Pathog. 2014 Jun-Jul;71-72:56-61. doi: 10.1016/j.micpath.2014.03.012. Epub 2014 Apr 16.
Sepsis induced by Staphylococcus aureus has worse outcome with the appearance of methicillin-resistant Staphylococcus aureus (MRSA) because of multi-resistance to a large group of antibiotics, which may lead to death from septic shock. Pathogenesis of S. aureus infections are involved in the production of a wide variety of virulence factors. MgrA, a noval global regulator, is a member of the MarR (multiple antibiotic resistance regulator)/SarA (staphylococcal accessory regulator A) family proteins, which plays a key role in regulating the expression of major virulence factors in S. aureus. In the present study, by using a murine model of sepsis, we investigated the role of mgrA in onset and progression of S. aureus induced sepsis. We found that mice inoculated with wild-type strain Newman had significantly higher mortality (p = 0.029), more weight lost, more bacterial load in blood, spleen and kidney, more intense inflammation response, and worse histopathology than mice inoculated with mgrA knockout strain. Our results has provided evidence that mgrA is a global regulator in S. aureus, and play an important role in S. aureus sepsis, could increase mortality and accelerate the onset and development of sepsis.
金黄色葡萄球菌引起的败血症由于对一大类抗生素的多重耐药性而出现耐甲氧西林金黄色葡萄球菌（MRSA）时，预后更差，可能导致感染性休克死亡。金黄色葡萄球菌感染的发病机制涉及多种毒力因子的产生。MgrA 是一种新型全局调节剂，是 MarR（多种抗生素耐药调节剂）/SarA（葡萄球菌辅助调节因子 A）家族蛋白的成员，在调节金黄色葡萄球菌主要毒力因子的表达中起着关键作用。在本研究中，我们通过使用败血症的小鼠模型，研究了 mgrA 在金黄色葡萄球菌诱导的败血症发病和进展中的作用。我们发现，与接种 mgrA 敲除株的小鼠相比，接种野生型 Newman 株的小鼠死亡率显著升高（p=0.029），体重减轻更多，血液、脾脏和肾脏中的细菌载量更多，炎症反应更剧烈，组织病理学更差。我们的结果提供了证据表明，mgrA 是金黄色葡萄球菌中的一个全局调节剂，在金黄色葡萄球菌败血症中发挥重要作用，可增加死亡率并加速败血症的发生和发展。
