Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, United States of America.
PLoS Pathog. 2011 Jul;7(7):e1002104. doi: 10.1371/journal.ppat.1002104. Epub 2011 Jul 7.
Staphylococcus aureus nasal colonization is an important risk factor for community and nosocomial infection. Despite the importance of S. aureus to human health, molecular mechanisms and host factors influencing nasal colonization are not well understood. To identify host factors contributing to nasal colonization, we collected human nasal secretions and analyzed their ability to promote S. aureus surface colonization. Some individuals produced secretions possessing the ability to significantly promote S. aureus surface colonization. Nasal secretions pretreated with protease no longer promoted S. aureus surface colonization, suggesting the involvement of protein factors. The major protein components of secretions were identified and subsequent analysis revealed that hemoglobin possessed the ability to promote S. aureus surface colonization. Immunoprecipitation of hemoglobin from nasal secretions resulted in reduced S. aureus surface colonization. Furthermore, exogenously added hemoglobin significantly decreased the inoculum necessary for nasal colonization in a rodent model. Finally, we found that hemoglobin prevented expression of the agr quorum sensing system and that aberrant constitutive expression of the agr effector molecule, RNAIII, resulted in reduced nasal colonization of S. aureus. Collectively our results suggest that the presence of hemoglobin in nasal secretions contributes to S. aureus nasal colonization.
金黄色葡萄球菌鼻腔定植是社区和医院感染的重要危险因素。尽管金黄色葡萄球菌对人类健康很重要,但影响鼻腔定植的分子机制和宿主因素仍未得到很好的理解。为了确定促进鼻腔定植的宿主因素,我们收集了人类鼻腔分泌物,并分析了它们促进金黄色葡萄球菌表面定植的能力。一些个体产生的分泌物具有显著促进金黄色葡萄球菌表面定植的能力。用蛋白酶预处理的鼻腔分泌物不再促进金黄色葡萄球菌表面定植,表明涉及蛋白质因素。鉴定了分泌物中的主要蛋白质成分,随后的分析表明血红蛋白具有促进金黄色葡萄球菌表面定植的能力。从鼻腔分泌物中免疫沉淀血红蛋白会导致金黄色葡萄球菌表面定植减少。此外,外源性添加血红蛋白可显著减少在啮齿动物模型中鼻腔定植所需的接种物。最后,我们发现血红蛋白阻止了 agr 群体感应系统的表达,并且 agr 效应分子 RNAIII 的异常组成型表达导致金黄色葡萄球菌鼻腔定植减少。总之,我们的研究结果表明,鼻腔分泌物中血红蛋白的存在有助于金黄色葡萄球菌的鼻腔定植。