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Internalization of Staphylococcus aureus by Human Keratinocytes

机译:人角质形成细胞对金黄色葡萄球菌的内在化

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Staphylococcus aureus is among the most important human pathogens and causes various superficial and systemic infections. The ability of S. aureus to be internalized by, and survive within, host cells, such as keratinocytes, may contribute to the development of persistent or chronic infections and may finally lead to deeper tissue infections or dissemination. To examine the mechanisms of internalization of S. aureus by keratinocytes, isogenic mutants lacking fibronectin-binding proteins (FnBPs), a recombinant protein consisting of the fibronectin-binding domain of S. aureus FnBPs, and an anti-α5β1 antibody were used in cocultures with immortalized keratinocytes and primary keratinocytes. We found that internalization of S. aureus by immortalized keratinocytes requires bacterial FnBPs and is mediated by the major fibronectin-binding integrin α5β1. In contrast to internalization by immortalized keratinocytes, internalization of S. aureus by primary keratinocytes could occur through FnBP-dependent and -independent pathways. S. aureus clumping factor B (ClfB), which was recently determined to bind to epithelial cells, was not involved in the uptake of this bacterium by keratinocytes. The identification of an alternate uptake pathway, which is independent of S. aureus FnBPs and host cell α5β1, has important implications for the design of therapies targeted to bacterial uptake by host cells.
机译:金黄色葡萄球菌是人类最重要的病原体之一,并引起各种浅表和全身感染。 S的能力。被宿主细胞(例如角质形成细胞)内化并在其中生存的金黄色葡萄球菌可能会导致持续性或慢性感染的发展,并最终导致更深的组织感染或传播。研究 S的内部化机制。角质形成细胞的金黄色葡萄球菌,是缺乏纤连蛋白结合蛋白(FnBPs)的等基因突变体,FnBPs是由 S的纤连蛋白结合域组成的重组蛋白。金黄色葡萄球菌FnBPs和抗α5β1抗体与永生化角质形成细胞和原代角质形成细胞共培养。我们发现 S的内部化。永生化角质形成细胞产生的金黄色葡萄球菌需要细菌FnBP,并由主要的纤连蛋白结合整联蛋白α5β1介导。与永生化角质形成细胞的内在化相反, S的内在化。原发性角质形成细胞的金黄色可能通过FnBP依赖性和非依赖性途径发生。 S。最近被确定与上皮细胞结合的金黄色素聚集因子B(ClfB)不参与角质形成细胞对该细菌的吸收。独立于 S的替代摄取途径的鉴定。金黄色葡萄球菌的FnBPs和宿主细胞α5β1对设计针对宿主细胞吸收细菌的疗法具有重要意义。

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