Institute of Medical Microbiology, Department of Infectiology, University Hospital of Münster, Münster, Germany.
Cell Microbiol. 2010 Dec;12(12):1746-64. doi: 10.1111/j.1462-5822.2010.01506.x.
Staphylococcus aureus and Staphylococcus epidermidis can cause serious chronic and recurrent infections that are difficult to eradicate. An important pathogenicity factor in these infections caused by S. aureus is its ability to be internalized by non-professional phagocytes thereby evading the host immune system and antibiotic treatment. Here, we report a novel mechanism involved in staphylococcal internalization by host cells, which is mediated by the major autolysin/adhesins Atl and AtlE from S. aureus and S. epidermidis respectively. In a flow cytometric internalization assay, atl and atlE mutants are significantly reduced in their capacities to be internalized by endothelial cells. Moreover, pre-incubation of endothelial cells with recombinant Atl dose-dependently inhibited internalization. As putative Atl-host cell receptor, the heat shock cognate protein Hsc70 was identified by mass spectrometry. The importance of Hsc70 in internalization was demonstrated by the inhibition of S. aureus internalization with anti-Hsc70 antibodies. In conclusion, this novel Atl- or AtlE-mediated internalization mechanism may represent a 'back-up' mechanism in S. aureus internalization, while it may represent the major or even sole mechanism involved in the internalization of coagulase-negative staphylococci and thus may play an important role in the pathogenesis of chronic and relapsing infections with these serious pathogens.
金黄色葡萄球菌和表皮葡萄球菌可引起难以根除的严重慢性和复发性感染。金黄色葡萄球菌引起的这些感染的一个重要致病性因素是其被非专业吞噬细胞内化的能力，从而逃避宿主免疫系统和抗生素治疗。在这里，我们报告了一个宿主细胞内化葡萄球菌的新机制，该机制由金黄色葡萄球菌和表皮葡萄球菌的主要自溶酶/黏附素 Atl 和 AtlE 介导。在流式细胞术内化测定中，atl 和 atlE 突变体的内化能力显著降低。此外，内皮细胞与重组 Atl 的预孵育可剂量依赖性地抑制内化。热休克同源蛋白 Hsc70 被鉴定为假定的 Atl-宿主细胞受体。用抗 Hsc70 抗体抑制金黄色葡萄球菌的内化证明了 Hsc70 在内化中的重要性。总之，这种新的 Atl 或 AtlE 介导的内化机制可能代表金黄色葡萄球菌内化的一种“备用”机制，而它可能代表凝固酶阴性葡萄球菌内化的主要甚至唯一机制，因此可能在这些严重病原体引起的慢性和复发性感染的发病机制中发挥重要作用。
