Differential expression and roles of Staphylococcus aureus virulence determinants during colonization and disease.
Differential expression and roles of Staphylococcus aureus virulence determinants during colonization and disease.
复制标题
金黄色葡萄球菌毒力决定因子在定植和致病过程中的差异表达及作用
DOI：
10.1128/mbio.02272-14
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发表时间：
2015-02-17
期刊：
影响因子：
6.4
通讯作者：
Sellman BR
中科院分区：
文献类型：
--
作者：
Jenkins A;Diep BA;Mai TT;Vo NH;Warrener P;Suzich J;Stover CK;Sellman BR
金黄色葡萄球菌是一种革兰氏阳性细菌，已知无症状地定殖于人类皮肤、鼻孔和胃肠道。定植个体发生金黄色葡萄球菌感染的风险增加，其范围从轻度皮肤和软组织感染到更严重的疾病，如心内膜炎、菌血症、败血症和骨髓炎。金黄色葡萄球菌感染不同的身体部位需要不同的毒力因子。在这项研究中，毒力基因的表达进行了分析，在两个金黄色葡萄球菌分离株在鼻腔定植，菌血症和心脏在脓毒症。选择这些模型来代表金黄色葡萄球菌从无症状定植者到侵袭性病原体的逐步进展。分析了23种推定的金黄色葡萄球菌毒力决定簇的表达，这些毒力决定簇代表蛋白质和碳水化合物粘附素、分泌毒素以及参与金属阳离子获得和免疫逃避的蛋白质。一致的上调sdrC，fnbA，fhuD，sstD，和hla的观察之间的转变殖民和侵入性病原体，这表明这些基因在葡萄球菌发病机制中的突出作用。最后，通过在动物模型中使用敲除突变体，将基因表达数据与基因在发病机制中的作用相关联。这些结果为金黄色葡萄球菌如何改变侵袭性和侵袭性病原体之间的毒力基因表达提供了见解。许多细菌，如金黄色葡萄球菌，无症状地定殖于人类皮肤和鼻道，但也可引起侵袭性疾病，如菌血症、肺炎、败血症和骨髓炎。本研究的目的是分析选定的金黄色葡萄球菌基因在细菌生活方式期间和作为侵入性病原体的表达差异，以深入了解细菌到病原体的转变以及细菌病原体如何适应宿主内的不同环境（例如，从鼻腔定植到侵入性病原体）。基因表达数据也被用来选择基因，构建敲除突变体，以评估几种蛋白质在鼻定植和致死菌血症中的作用。这些结果不仅提供了深入了解参与金黄色葡萄球菌疾病发病机制的因素，而且还提供了潜在的治疗靶点。
Staphylococcus aureus is a Gram-positive, commensal bacterium known to asymptomatically colonize the human skin, nares, and gastrointestinal tract. Colonized individuals are at increased risk for developing S. aureus infections, which range from mild skin and soft tissue infections to more severe diseases, such as endocarditis, bacteremia, sepsis, and osteomyelitis. Different virulence factors are required for S. aureus to infect different body sites. In this study, virulence gene expression was analyzed in two S. aureus isolates during nasal colonization, bacteremia and in the heart during sepsis. These models were chosen to represent the stepwise progression of S. aureus from an asymptomatic colonizer to an invasive pathogen. Expression of 23 putative S. aureus virulence determinants, representing protein and carbohydrate adhesins, secreted toxins, and proteins involved in metal cation acquisition and immune evasion were analyzed. Consistent upregulation of sdrC, fnbA, fhuD, sstD, and hla was observed in the shift between colonization and invasive pathogen, suggesting a prominent role for these genes in staphylococcal pathogenesis. Finally, gene expression data were correlated to the roles of the genes in pathogenesis by using knockout mutants in the animal models. These results provide insights into how S. aureus modifies virulence gene expression between commensal and invasive pathogens. Many bacteria, such as Staphylococcus aureus, asymptomatically colonize human skin and nasal passages but can also cause invasive diseases, such as bacteremia, pneumonia, sepsis, and osteomyelitis. The goal of this study was to analyze differences in the expression of selected S. aureus genes during a commensal lifestyle and as an invasive pathogen to gain insight into the commensal-to-pathogen transition and how a bacterial pathogen adapts to different environments within a host (e.g., from nasal colonization to invasive pathogen). The gene expression data were also used to select genes for which to construct knockout mutants to assess the role of several proteins in nasal colonization and lethal bacteremia. These results not only provide insight into the factors involved in S. aureus disease pathogenesis but also provide potential therapeutic targets.