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葡萄球菌菌株在诱导内皮细胞炎症反应的能力上有很大差异。

Staphylococcal strains vary greatly in their ability to induce an inflammatory response in endothelial cells.

机构信息

Institute of Medical Microbiology, University Hospital of Münster, Domagkstrasse 10, D-48149 Münster, Germany.

出版信息

J Infect Dis. 2010 Mar 15;201(6):871-80. doi: 10.1086/651023.

DOI:10.1086/651023
PMID:20132035
Abstract

BACKGROUND

Staphylococcus aureus is an important human pathogen of endovascular diseases that can take an acute destructive course and/or develop into a chronic infection with a high rate of relapse. Despite good activity of the appropriate antimicrobial substances in vitro, these infections are often difficult to treat, perhaps because of the complex infection process of endovascular tissue.

METHODS

We used the microarray technique to analyze the response of endothelial cells to different S. aureus strains, including highly virulent isolates (6850 and ST239); the Cowan I strain, which has a nonfunctioning accessory gene regulator (agr) quorum-sensing system; and various clinical isolates.

RESULTS

All tested strains were equally invasive in endothelial cells and were found intracellularly, but they differed greatly in their ability to induce inflammation. Wild-type isolates (6850 and ST239) up-regulated a huge number of genes, including many genes involved in innate immunity. By contrast, Cowan I, which failed to express important virulence factors related to the agr system (eg, alpha-toxin and proteases), did not induce these dramatic changes in endothelial gene expression. Similar results were obtained with clinical isolates.

CONCLUSION

Given that agr-defective strains are commonly recovered during colonization and infection, agr deficiency might represent a strategy of S. aureus to hide intracellularly without provoking the host immune system and causing relapsing infections.

摘要

背景

金黄色葡萄球菌是一种重要的人类病原体,可引起血管内疾病,其病程可以是急性破坏性的,也可以发展为慢性感染,且复发率较高。尽管体外适当的抗菌物质具有良好的活性,但这些感染通常难以治疗,这可能是由于血管内组织的复杂感染过程所致。

方法

我们使用微阵列技术分析了内皮细胞对不同金黄色葡萄球菌菌株的反应,包括高毒力分离株(6850 和 ST239);缺乏功能辅助基因调控子(agr)群体感应系统的 Cowan I 株;以及各种临床分离株。

结果

所有测试的菌株在血管内皮细胞中均具有相同的侵袭性,并在细胞内被发现,但它们在诱导炎症的能力上有很大差异。野生型分离株(6850 和 ST239)上调了大量基因,包括许多与先天免疫相关的基因。相比之下,无法表达与 agr 系统相关的重要毒力因子(如α-毒素和蛋白酶)的 Cowan I 株则不会引起内皮细胞基因表达的这些显著变化。临床分离株也得到了类似的结果。

结论

鉴于 agr 缺陷株在定植和感染期间通常会被回收,agr 缺陷可能代表了金黄色葡萄球菌的一种策略,即通过不引起宿主免疫系统的反应并导致反复感染,从而在细胞内隐匿。

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