Staphylococcus aureus Transporters Hts, Sir, and Sst Capture Iron Liberated from Human Transferrin by Staphyloferrin A, Staphyloferrin B, and Catecholamine Stress Hormones, Respectively, and Contribute to Virulence
Staphylococcus aureus Transporters Hts, Sir, and Sst Capture Iron Liberated from Human Transferrin by Staphyloferrin A, Staphyloferrin B, and Catecholamine Stress Hormones, Respectively, and Contribute to Virulence
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DOI：
10.1128/iai.00117-11
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发表时间：
2011-06-01
影响因子：
3.1
通讯作者：
Heinrichs, David E.
中科院分区：
文献类型：
--
作者：
Beasley, Federico C.;Marolda, Cristina L.;Heinrichs, David E.
金黄色葡萄球菌是血液、呼吸道、皮肤和软组织感染的常见原因。在血液中，铁结合糖蛋白转铁蛋白循环为全身细胞提供铁，但其铁结合特性使其成为先天免疫的重要组成部分。铁载体对铁具有很高的亲和力，在许多情况下，它可以从转铁蛋白中去除铁，作为促进细菌病原体增殖的一种手段，这是公认的。还证实儿茶酚胺激素可以干扰转铁蛋白的铁结合特性，从而使感染性细菌进入这个铁池。本研究表明，金黄色葡萄球菌可以分别通过转运蛋白HTS和SIR使用两种羧酸型铁载体中的任何一种，即葡萄铁蛋白A和葡萄铁蛋白B来访问转铁蛋白铁库。在儿茶酚胺存在的情况下，在血清中或在全转铁蛋白存在的情况下，产生葡萄铁蛋白的金黄色葡萄球菌的生长没有促进作用。然而，儿茶酚胺显著促进葡萄铁蛋白缺陷型金黄色葡萄球菌在人血清中或在人全转铁蛋白存在下的生长。进一步证明，SST转运体对于这一活动以及细菌邻苯二酚铁载体的利用是必不可少的。底物结合蛋白SSTD与发酵儿茶酚胺和儿茶酚铁载体相互作用，亲和力从低到亚微摩尔。用野生型金黄色葡萄球菌和等基因突变体静脉攻击小鼠的实验表明，HTS、SIR和SST运输系统的组合是金黄色葡萄球菌完全毒力所必需的。
Staphylococcus aureus is a frequent cause of bloodstream, respiratory tract, and skin and soft tissue infections. In the bloodstream, the iron-binding glycoprotein transferrin circulates to provide iron to cells throughout the body, but its iron-binding properties make it an important component of innate immunity. It is well established that siderophores, with their high affinity for iron, in many instances can remove iron from transferrin as a means to promote proliferation of bacterial pathogens. It is also established that catecholamine hormones can interfere with the iron-binding properties of transferrin, thus allowing infectious bacteria access to this iron pool. The present study demonstrates that S. aureus can use either of two carboxylate-type siderophores, staphyloferrin A and staphyloferrin B, via the transporters Hts and Sir, respectively, to access the transferrin iron pool. Growth of staphyloferrin-producing S. aureus in serum or in the presence of holotransferrin was not enhanced in the presence of catecholamines. However, catecholamines significantly enhanced the growth of staphyloferrin-deficient S. aureus in human serum or in the presence of human holotransferrin. It was further demonstrated that the Sst transporter was essential for this activity as well as for the utilization of bacterial catechol siderophores. The substrate binding protein SstD was shown to interact with ferrated catecholamines and catechol siderophores, with low to submicromolar affinities. Experiments involving mice challenged intravenously with wild-type S. aureus and isogenic mutants demonstrated that the combination of Hts, Sir, and Sst transport systems was required for full virulence of S. aureus.