Genetic requirements for Staphylococcus aureus abscess formation and persistence in host tissues
Genetic requirements for Staphylococcus aureus abscess formation and persistence in host tissues
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DOI：
10.1096/fj.09-135467
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发表时间：
2009-10-01
期刊：
影响因子：
4.8
通讯作者：
Missiakas, Dominique M.
中科院分区：
文献类型：
--
作者：
Cheng, Alice G.;Kim, Hwan Keun;Missiakas, Dominique M.
金黄色葡萄球菌感染与脓肿形成和细菌持续存在有关;然而，使这种生活方式成为可能的基因尚不清楚。我们在这里表明，在小鼠静脉感染后，S。金黄色葡萄球菌迅速传播到器官组织中，并引起脓肿病变，该脓肿病变在数周内发展，但不能被宿主清除。葡萄球菌在脓肿病灶的中心作为群落生长，并被假包膜包围，将病原体与免疫细胞隔开。通过测试细胞壁锚定表面蛋白基因中的插入变体，我们能够推断出这些分子发挥功能的阶段。纤维蛋白原结合蛋白ClfA和ClfB是葡萄球菌播散早期所必需的。血红素清除因子IsdA和IsdB以及SdrD和蛋白A是脓肿形成所必需的。包膜相关蛋白Emp和Eap是脓肿形成所必需的，也是导致脓肿持续存在的原因。荧光显微镜检查显示Eap沉积在假包膜内，而Emp定位在葡萄球菌脓肿社区内。针对脓肿相关蛋白的抗体产生了针对葡萄球菌脓肿形成的疫苗保护。因此，葡萄球菌利用包膜蛋白在一个独立的阶段的发展计划，使脓肿的形成和细菌的持久性在宿主组织。Cheng，中国山核桃A. G.，Kim，H. K.，Burts，M. L.，Krausz，T.，Schneewind，O.，米萨卡斯湾M.金黄色葡萄球菌脓肿形成和在宿主组织中持续存在的遗传要求。FASEB J.23，3393-3404（2009）. www.fasebj.org
Staphylococcus aureus infections are associated with abscess formation and bacterial persistence; however, the genes that enable this lifestyle are not known. We show here that following intravenous infection of mice, S. aureus disseminates rapidly into organ tissues and elicits abscess lesions that develop over weeks but cannot be cleared by the host. Staphylococci grow as communities at the center of abscess lesions and are enclosed by pseudocapsules, separating the pathogen from immune cells. By testing insertional variants in genes for cell wall-anchored surface proteins, we are able to infer the stage at which these molecules function. Fibrinogen-binding proteins ClfA and ClfB are required during the early phase of staphylococcal dissemination. The heme scavenging factors IsdA and IsdB, as well as SdrD and protein A, are necessary for abscess formation. Envelope-associated proteins, Emp and Eap, are either required for abscess formation or contribute to persistence. Fluorescence microscopy revealed Eap deposition within the pseudocapsule, whereas Emp was localized within staphylococcal abscess communities. Antibodies directed against envelope-associated proteins generated vaccine protection against staphylococcal abscess formation. Thus, staphylococci employ envelope proteins at discrete stages of a developmental program that enables abscess formation and bacterial persistence in host tissues. Cheng, A. G., Kim, H. K., Burts, M. L., Krausz, T., Schneewind, O., Missiakas, D. M. Genetic requirements for Staphylococcus aureus abscess formation and persistence in host tissues. FASEB J. 23, 3393-3404 ( 2009). www.fasebj.org