title: Involvement of SirABC in iron-siderophore import in Staphylococcus aureus.
abstract: Staphylococcus aureus SirA was previously identified as a lipoprotein, and SirB and SirC are thought to encode the transmembrane domains of an ABC transporter. Sir proteins show similarity to iron-siderophore transporters in several bacteria. Here, we show that the iron-regulated sirABC operon is divergently transcribed from the sbn operon that encodes enzymes involved in the synthesis of staphylobactin, a recently described siderophore produced by S. aureus. Mutation of either sirA or sirB increased the resistance of iron-starved S. aureus to streptonigrin and resulted in compromised growth in iron-restricted, but not iron-rich, media. We also demonstrated that sirA and sirB mutants are compromised in the ability to transport iron complexed to staphylobactin but are not compromised for uptake of other iron complexes, such as ferric hydroxamates, ferric enterobactin, or ferric citrate. SirA- and SirB-deficient S. aureus, however, retain the ability to produce staphylobactin. Moreover, we found that transcription from the sbn operon was increased, relative to the wild type, in both sirA and sirB knockout strains, likely in response to an increased level of iron starvation in these cells. These results provide evidence of a role for these proteins in iron import in S. aureus and for full fitness of the bacterium in iron-restricted environments and demonstrate a function for S. aureus genes encoding proteins involved in the transport of an endogenously produced siderophore.
authors.affiliation: Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada N6A 5C1.
authors.forename: Suzanne E
authors.initials: SE
authors.lastname: Dale
authors.forename: M Tom
authors.initials: MT
authors.lastname: Sebulsky
authors.forename: David E
authors.initials: DE
authors.lastname: Heinrichs
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001692:Biological Transport; D003470:Culture Media; D005290:Ferric Compounds / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D007501:Iron / Q000378:metabolism*; D009154:Mutation; D009876:Operon; D017262:Siderophores / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D018528:ATP-Binding Cassette Transporters; D001426:Bacterial Proteins; D003470:Culture Media; D005290:Ferric Compounds; D017262:Siderophores; C118128:SirA protein, Staphylococcus; D007501:Iron