Wang Lin, Bi Chongwei, Wang Tiedong, Xiang Hua, Chen Fuguang, Hu Jinping, Liu Bingrun, Cai Hongjun, Zhong Xiaobo, Deng Xuming, Wang Dacheng
Key Laboratory of Zoonosis Research, Ministry of Education/Institute of Zoonosis/College of Veterinary Medicine, Jilin University, Changchun 130062, China.
College of Animal Science, Jilin University, Changchun 130062, China.
Pathog Dis. 2015 Aug;73(6):ftv042. doi: 10.1093/femspd/ftv042. Epub 2015 Jun 7.
Sortase A (SrtA) is a cysteine transpeptidase and virulence factor from Staphylococcus aureus (S. aureus) that catalyses the attachment and display of surface proteins on the cell wall, thereby mediating bacterial adhesion to host tissues, host-cell entry and evasion of the immune response. As a result, SrtA has become an important target in the development of therapies for S. aureus infections. In this study, we used the new reference strain S. aureus Newman D2C to investigate the role of SrtA in a murine model of bloodstream infection, when the impact of coagulase and haemolysin is excluded. The results suggested that deletion of SrtA reduced the bacterial burden on the heart, liver and kidneys by blunting the host proinflammatory cytokine response at an early point in infection. Kidneys, but not heart or liver, formed abscesses on the sixth day following non-lethal infection, and this effect was diminished by SrtA mutation. These findings indicate that SrtA is a determining virulence factor in lethality and formation of renal abscesses in mice followed by S. aureus bloodstream infection. We have thus established a convenient in vitro and mouse model for developing SrtA-targeted therapeutic strategies.
分选酶A（SrtA）是一种来自金黄色葡萄球菌（S. aureus）的半胱氨酸转肽酶和毒力因子，它催化表面蛋白附着并展示在细胞壁上，从而介导细菌与宿主组织的黏附、进入宿主细胞并逃避免疫反应。因此，SrtA已成为开发金黄色葡萄球菌感染治疗方法的重要靶点。在本研究中，我们使用新的参考菌株金黄色葡萄球菌纽曼D2C，在排除凝固酶和溶血素影响的情况下，研究SrtA在血流感染小鼠模型中的作用。结果表明，SrtA的缺失通过在感染早期减弱宿主促炎细胞因子反应，降低了心脏、肝脏和肾脏的细菌负荷。在非致死性感染后的第六天，肾脏（而非心脏或肝脏）形成了脓肿，而这种效应因SrtA突变而减弱。这些发现表明，SrtA是金黄色葡萄球菌血流感染后小鼠致死率和肾脓肿形成的决定性毒力因子。我们因此建立了一个方便的体外和小鼠模型，用于开发针对SrtA的治疗策略。
