Molecular Signaling Section, Laboratory of Molecular Immunology, NIAID, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Biol Chem. 2011 Feb 18;286(7):5069-77. doi: 10.1074/jbc.M110.195180. Epub 2010 Dec 7.
There are few examples of host signals that are beneficial to bacteria during infection. Here we found that 31 out of 42 host immunoregulatory chemokines were able to induce release of the virulence factor protein A (SPA) from a strain of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA). Detailed study of chemokine CXCL9 revealed that SPA release occurred through a post-translational mechanism and was inversely proportional to bacterial density. CXCL9 bound specifically to the cell membrane of CA-MRSA, and the related SPA-releasing chemokine CXCL10 bound to both cell wall and cell membrane. Clinical samples from patients infected with S. aureus and samples from a mouse model of CA-MRSA skin abscess all contained extracellular SPA. Further, SPA-releasing chemokines were present in mouse skin lesions infected with CA-MRSA. Our data identify a potential new mode of immune evasion, in which the pathogen exploits a host defense factor to release a virulence factor; moreover, chemokine binding may serve a scavenging function in immune evasion by S. aureus.
在感染过程中，宿主信号几乎没有对细菌有益的例子。在这里，我们发现 42 种宿主免疫调节趋化因子中有 31 种能够诱导社区相关耐甲氧西林金黄色葡萄球菌（CA-MRSA）菌株释放毒力因子蛋白 A（SPA）。对趋化因子 CXCL9 的详细研究表明，SPA 的释放是通过翻译后机制发生的，并且与细菌密度成反比。CXCL9 特异性结合 CA-MRSA 的细胞膜，相关的 SPA 释放趋化因子 CXCL10 结合细胞壁和细胞膜。感染金黄色葡萄球菌的患者的临床样本和 CA-MRSA 皮肤脓肿的小鼠模型样本均含有细胞外 SPA。此外，CA-MRSA 感染的小鼠皮肤病变中存在释放 SPA 的趋化因子。我们的数据确定了一种潜在的新免疫逃避模式，其中病原体利用宿主防御因子释放毒力因子；此外，趋化因子结合可能在金黄色葡萄球菌的免疫逃避中发挥清除功能。
