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

被引:108
作者
Beasley, Federico C. [1 ]
Marolda, Cristina L. [1 ]
Cheung, Johnson [1 ]
Buac, Suzana [1 ]
Heinrichs, David E. [1 ]
机构
[1] Univ Western Ontario, Dept Microbiol & Immunol, London, ON N6A 5C1, Canada
基金
加拿大健康研究院;
关键词
BACILLUS-SUBTILIS; ESCHERICHIA-COLI; HEME-IRON; SIDEROPHORE PRODUCTION; STRUCTURAL GENE; NOREPINEPHRINE; GROWTH; IDENTIFICATION; BINDING; EPIDERMIDIS;
D O I
10.1128/IAI.00117-11
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:2345 / 2355
页数:11
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