Staphylococcal Strains Vary Greatly in Their Ability to Induce an Inflammatory Response in Endothelial Cells
Staphylococcal Strains Vary Greatly in Their Ability to Induce an Inflammatory Response in Endothelial Cells
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DOI：
10.1086/651023
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发表时间：
2010-03-15
影响因子：
6.4
通讯作者：
Loeffler, Bettina
中科院分区：
文献类型：
--
作者：
Grundmeier, Matthias;Tuchscherr, Lorena;Loeffler, Bettina
背景资料。金黄色葡萄球菌是一种重要的人类血管内疾病的病原体，它可以采取急性破坏性过程和/或发展为慢性感染，复发率高。尽管合适的抗菌物质在体外具有良好的活性，但这些感染往往难以治疗，可能是因为血管内组织的复杂感染过程。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株的反应，包括高毒力分离株(6850和ST239)、具有不起作用的辅助基因调节(AGR)群体传感系统的考万I株以及各种临床分离株。所有测试菌株在内皮细胞中的侵袭性相同，并在细胞内发现，但它们在诱导炎症的能力方面存在很大差异。野生型分离株(6850和ST239)上调了大量基因的表达，包括许多与先天免疫有关的基因。相比之下，Cowan I不表达与AGR系统相关的重要毒力因子(如α-毒素和蛋白酶)，也没有诱导内皮基因表达的这些戏剧性变化。临床分离株也得到了类似的结果。由于agr缺陷菌株通常在定植和感染过程中被恢复，agr缺陷可能代表了金黄色葡萄球菌的一种策略，即隐藏在细胞内而不刺激宿主免疫系统并导致复发感染。
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.