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Infection and Immunity, January 2004, p. 29-37, Vol. 72, No. 1
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.1.29-37.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

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

Suzanne E. Dale,1 Amanda Doherty-Kirby,2 Gilles Lajoie,2 and David E. Heinrichs1,3*

Departments of Microbiology and Immunology,1 Biochemistry, University of Western Ontario, London, Ontario, Canada N6A 5C1,2 Lawson Health Research Institute, London, Ontario, Canada N6A 4V23

Received 17 April 2003/ Returned for modification 10 June 2003/ Accepted 16 September 2003

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.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada N6A 5C1. Phone: (519) 661-3984. Fax: (519) 661-3499. E-mail: deh{at}uwo.ca.

Editor: V. J. DiRita

Infection and Immunity, January 2004, p. 29-37, Vol. 72, No. 1
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.1.29-37.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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