Institutes of Medical Microbiology, Center of Clinical Research, University Hospital of Münster, Münster, Germany.
J Infect Dis. 2010 Oct 1;202(7):1031-40. doi: 10.1086/656047.
Staphylococcus aureus is an important human pathogen of endovascular diseases, which can take a chronic course with a high relapse rate despite antimicrobial treatment. Thus far, persistent and antibiotic-refractory infections have been largely associated with a subpopulation of S. aureus, the small-colony variants (SCVs).
In this work, we used endothelial cells to investigate infection with the highly virulent wild-type isolate (6850), 2 stable isogenic SCV phenotypes (hemB mutant IIb13 and JB1), and the complemented mutant.
All strains were highly invasive in endothelial cells but largely differed in host response induction. Microarray analysis showed that wild-type phenotypes up-regulated a large number of endothelial genes (including genes involved in innate immunity), whereas the SCVs did not cause these dramatic changes. The inflammatory response and cytotoxicity were strongest shortly after infection and largely decreased within the following days, which was accompanied by a fast elimination of intracellular wild-type bacteria. By contrast, SCVs survived within endothelial cells at high numbers.
S. aureus intracellular persistence via the development of an adapted subpopulation of SCVs most likely represents an important strategy of S. aureus to hide within the host cells, which could be a reservoir for chronic infections.
金黄色葡萄球菌是一种重要的人类血管内疾病病原体，尽管进行了抗菌治疗，但其仍可能呈慢性病程且复发率高。迄今为止，持续性和抗生素难治性感染在很大程度上与金黄色葡萄球菌的一个亚群（小菌落变异株，SCVs）有关。
在这项工作中，我们使用内皮细胞来研究高毒力野生型分离株（6850）、2 种稳定的同源 SCV 表型（hemB 突变体 IIb13 和 JB1）和互补突变体的感染情况。
所有菌株在内皮细胞中均具有很强的侵袭性，但在诱导宿主反应方面存在很大差异。微阵列分析显示，野生型表型上调了大量内皮细胞基因（包括参与固有免疫的基因），而 SCVs 则不会引起这些显著变化。炎症反应和细胞毒性在感染后不久最强，并在随后的几天内大大降低，同时伴有细胞内野生型细菌的快速清除。相比之下，SCVs 在内皮细胞中以高数量存活。
金黄色葡萄球菌通过形成适应性 SCV 亚群在细胞内持续存在，这可能是金黄色葡萄球菌隐藏在宿主细胞内的一种重要策略，这可能是慢性感染的一个储库。
