Role of Siderophore Biosynthesis in Virulence of <i>Staphylococcus aureus</i> : Identification and Characterization of Genes Involved in Production of a Siderophore

<jats:title>ABSTRACT</jats:title> <jats:p> Molecular determinants underlying the production of siderophores in the human and animal pathogen <jats:italic>Staphylococcus aureus</jats:italic> and the contribution of siderophore production to the virulence of this bacterium have, until now, remained undefined. Here, we show that <jats:italic>S. aureus</jats:italic> 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 <jats:italic>sbn</jats:italic> and situated between <jats:italic>sirABC</jats:italic> and <jats:italic>galE</jats:italic> on the <jats:italic>S. aureus</jats:italic> chromosome, that is involved in the production of a siderophore. Mutation of the <jats:italic>sbnE</jats:italic> 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 <jats:italic>sbnE</jats:italic> into <jats:italic>sbnE</jats:italic> mutants complemented the inability of the mutants to produce the siderophore. <jats:italic>sbnE</jats:italic> 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 <jats:italic>sbnE</jats:italic> mutant was compromised in a murine kidney abscess model of <jats:italic>S. aureus</jats:italic> infection, illustrating the importance of siderophore production to the pathogenicity of <jats:italic>S. aureus. sbn</jats:italic> genes were present in all <jats:italic>S. aureus</jats:italic> strains tested (and all <jats:italic>S. aureus</jats:italic> genome sequences) but were undetectable in any of the 13 coagulase-negative staphylococci tested, including <jats:italic>Staphylococcus epidermidis</jats:italic> . </jats:p>