A novel staphylococcal internalization mechanism involves the major autolysin Atl and heat shock cognate protein Hsc70 as host cell receptor
A novel staphylococcal internalization mechanism involves the major autolysin Atl and heat shock cognate protein Hsc70 as host cell receptor
复制标题
DOI：
10.1111/j.1462-5822.2010.01506.x
复制
发表时间：
2010-12-01
影响因子：
3.4
通讯作者：
Heilmann, Christine
中科院分区：
文献类型：
--
作者：
Hirschhausen, Nina;Schlesier, Tim;Heilmann, Christine
金黄色葡萄球菌和表皮葡萄球菌可引起严重的慢性和复发性感染，难以根除。是引起这些感染的重要致病因子。金黄色葡萄球菌的另一个特征是它能够被非专职吞噬细胞内化，从而逃避宿主免疫系统和抗生素治疗。在这里，我们报告了一种新的机制，参与葡萄球菌内化的宿主细胞，这是介导的主要自溶素/粘附素Atl和ESTE从S。金黄色葡萄球菌和表皮细胞。在流式细胞仪内化测定中，atl和atlE突变体被内皮细胞内化的能力显著降低。此外，用重组Atl预孵育内皮细胞剂量依赖性地抑制内化。热休克同源蛋白Hsc 70作为推测的热休克-宿主细胞受体，通过质谱鉴定。Hsc 70在内化中的重要性通过抑制S.金黄色葡萄球菌内化与抗Hsc 70抗体。总之，这种新的Atl-或AtoE-介导的内化机制可能代表了S.金黄色葡萄球菌的内化，而它可能是主要的，甚至是唯一的机制，参与凝固酶阴性葡萄球菌的内化，因此可能发挥重要作用的慢性和复发性感染与这些严重的病原体的发病机制。
P>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.