Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee.
J Infect Dis. 2014 Jun 1;209(11):1764-72. doi: 10.1093/infdis/jit817. Epub 2013 Dec 13.
Staphylococcus aureus is a Gram-positive pathogen responsible for tremendous morbidity and mortality. As with most bacteria, S. aureus requires iron to cause disease, and it can acquire iron from host hemoglobin. The current model for staphylococcal hemoglobin-iron acquisition proposes that S. aureus binds hemoglobin through the surface-exposed hemoglobin receptor IsdB. IsdB removes heme from bound hemoglobin and transfers this cofactor to other proteins of the Isd system, which import and degrade heme to release iron in the cytoplasm. Here we demonstrate that the individual components of the Isd system are required for growth on low nanomolar concentrations of hemoglobin as a sole source of iron. An in-depth study of hemoglobin binding by IsdB revealed key residues that are required for hemoglobin binding. Further, we show that these residues are necessary for heme extraction from hemoglobin and growth on hemoglobin as a sole iron source. These processes are found to contribute to the pathogenicity of S. aureus in a murine model of infection. Together these results build on the model for Isd-mediated hemoglobin binding and heme-iron acquisition during the pathogenesis of S. aureus infection.
金黄色葡萄球菌是一种革兰氏阳性病原体，可导致巨大的发病率和死亡率。与大多数细菌一样，金黄色葡萄球菌需要铁才能致病，它可以从宿主血红蛋白中获取铁。目前的金黄色葡萄球菌血红蛋白铁摄取模型提出，金黄色葡萄球菌通过表面暴露的血红蛋白受体 IsdB 结合血红蛋白。IsdB 从结合的血红蛋白中去除血红素，并将该辅因子转移到 Isd 系统的其他蛋白，这些蛋白将血红素导入并降解以在细胞质中释放铁。在这里，我们证明了 Isd 系统的各个组件在低纳摩尔浓度的血红蛋白作为唯一铁源的情况下生长是必需的。对 IsdB 与血红蛋白结合的深入研究揭示了血红蛋白结合所必需的关键残基。此外，我们还表明，这些残基对于从血红蛋白中提取血红素以及仅以血红蛋白作为铁源生长是必需的。这些过程被发现有助于金黄色葡萄球菌在感染的小鼠模型中的致病性。这些结果建立在 Isd 介导的金黄色葡萄球菌感染发病机制中的血红蛋白结合和血红素铁摄取模型的基础上。
