Role of siderophore biosynthesis in virulence of Staphylococcus aureus:: Identification and characterization of genes involved in production of a siderophore
Role of siderophore biosynthesis in virulence of Staphylococcus aureus:: Identification and characterization of genes involved in production of a siderophore
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DOI：
10.1128/iai.72.1.29-37.2004
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发表时间：
2004-01-01
影响因子：
3.1
通讯作者：
Heinrichs, DE
中科院分区：
文献类型：
--
作者：
Dale, SE;Doherty-Kirby, A;Heinrichs, DE
到目前为止，人类和动物病原体金黄色葡萄球菌中铁载体产生的分子决定因素以及铁载体产生对该细菌毒力的贡献仍未明确。在这里，我们展示了金黄色葡萄球菌菌株RN6390和Newman在细胞缺铁时产生铁载体。我们进一步鉴定并鉴定了一个由9个基因组成的铁调控操纵子，编号为sbn，位于金黄色葡萄球菌染色体上的sirABC和galE之间，参与铁载体的产生。在RN6390和Newman中，sbnE基因的突变消除了这些菌株在铁限制生长条件下产生铁载体的能力，而在sbnE突变体中引入多拷贝sbnE弥补了突变体无法产生铁载体的缺陷。与野生型相比，RN6390和Newman背景下的sbnE突变体在限铁培养基中表现出严重的生长缺陷，而在富铁培养基中则没有这种缺陷。补充突变体显示出在铁限制下恢复的生长能力。我们进一步发现，sbnE突变体在金黄色葡萄球菌感染的小鼠肾脓肿模型中被破坏，这说明了铁载体的产生对金黄色葡萄球菌致病性的重要性。sbn基因存在于所有金黄色葡萄球菌测试菌株（和所有金黄色葡萄球菌基因组序列）中，但在13种凝固酶阴性葡萄球菌测试中未检测到，包括表皮葡萄球菌。
Molecular determinants underlying the production of siderophores in the human and animal pathogen Staphylococcus aureus and the contribution of siderophore production to the virulence of this bacterium have, until now, remained undefined. Here, we show that S. aureus strains RN6390 and Newman produce siderophore when the cells are starved for iron. We further identified and characterized a nine-gene, iron-regulated operon, designated sbn and situated between sirABC and galE on the S. aureus chromosome, that is involved in the production of a siderophore. Mutation of the sbnE gene, in both RN6390 and Newman, eliminates the ability of these strains to produce a siderophore under iron-limited growth conditions, while introduction of multicopy sbnE into sbnE mutants complemented the inability of the mutants to produce the siderophore. sbnE mutants, in both the RN6390 and Newman backgrounds, displayed a drastic growth deficiency, compared to the wild type, in iron-restricted growth medium, whereas no such deficiency was observed during growth in iron-replete medium. Complemented mutants showed a restored ability to grow under iron restriction. We further showed that an sbnE mutant was compromised in a murine kidney abscess model of S. aureus infection, illustrating the importance of siderophore production to the pathogenicity of S. aureus. sbn genes were present in all S. aureus strains tested (and all S. aureus genome sequences) but were undetectable in any of the 13 coagulase-negative staphylococci tested, including Staphylococcus epidermidis.