IsdB-dependent hemoglobin binding is required for acquisition of heme by Staphylococcus aureus.
IsdB-dependent hemoglobin binding is required for acquisition of heme by Staphylococcus aureus.
复制标题
DOI：
10.1093/infdis/jit817
复制
发表时间：
2014-06
期刊：
影响因子：
--
通讯作者：
Gleb Pishchany;J. Sheldon;C. Dickson;Md Tauqeer Alam;T. Read;D. Gell;D. Heinrichs;Eric P. Skaar
中科院分区：
文献类型：
--
作者：
Gleb Pishchany;J. Sheldon;C. Dickson;Md Tauqeer Alam;T. Read;D. Gell;D. Heinrichs;Eric P. Skaar
金黄色葡萄球菌是一种革兰氏阳性病原体，造成巨大的发病率和死亡率。与大多数细菌一样，S。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得铁。目前的葡萄球菌血红蛋白-铁获取模型提出S。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系统的其他蛋白质中，这些蛋白质输入并降解血红素以在细胞质中释放铁。在这里，我们证明了Isd系统的各个组成部分是生长所需的低纳摩尔浓度的血红蛋白作为唯一的铁源。通过IsdB对血红蛋白结合的深入研究揭示了血红蛋白结合所需的关键残基。此外，我们表明，这些残留物是必要的血红素提取血红蛋白和血红蛋白作为唯一的铁源的增长。这些过程被发现有助于致病性S。金黄色葡萄球菌感染的小鼠模型。这些结果共同建立了在S.金黄色葡萄球菌感染。
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.