title: Haemin represses the haemolytic activity of Staphylococcus aureus in an Sae-dependent manner.
abstract: Staphylococcus aureus is a major human pathogen and a common cause of nosocomial infections. This facultative pathogen produces a large arsenal of virulence factors, including the haemolysins, which allow the bacterium to lyse erythrocytes and thereby release large amounts of the haem-containing haemoglobin. The released haem is thought to be the main iron source of this organism during the course of infection, and is considered to be crucial for bacterial proliferation in vivo. High concentrations of haem and its degradation products, on the other hand, are known to be toxic for S. aureus, making it essential for the pathogen to tightly control haem release from red blood cells. Here we show that S. aureus responds to haemin by downregulating the expression of haemolysins. Subinhibitory concentrations of haemin were found to significantly reduce transcription of the haemolysin genes hlb (encoding β-haemolysin) and hlgA (encoding the S-class component of γ-haemolysin), while hla (encoding α-haemolysin) and RNAIII (encoding δ-haemolysin) transcription did not appear to be affected. The presence of haemin also reduced the haemolytic potential of the supernatants of S. aureus LS1 cultures. Inactivation of the sae locus in LS1 abolished the haemin effect on the transcription of haemolysin genes, indicating that the two-component regulatory system is required for this regulatory effect. Iron limitation, on the other hand, was found to induce the expression of haemolysins, and this effect was again abolished in the sae mutant, indicating that S. aureus modulates its haemolysin production in response to iron and haem availability in an Sae-dependent manner.
authors.affiliation: Institute of Medical Microbiology and Hygiene, University of Saarland Hospital, Homburg/Saar, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Schmitt
authors.affiliation: Institute of Medical Microbiology and Hygiene, University of Saarland Hospital, Homburg/Saar, Germany.
authors.forename: Insa
authors.initials: I
authors.lastname: Joost
authors.affiliation: Vanderbilt University Medical Center, Department of Pathology, Microbiology and Immunology, Nashville, TN, USA.
authors.forename: Eric P
authors.initials: EP
authors.lastname: Skaar
authors.affiliation: Institute of Medical Microbiology and Hygiene, University of Saarland Hospital, Homburg/Saar, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Herrmann
authors.affiliation: Institute of Medical Microbiology and Hygiene, University of Saarland Hospital, Homburg/Saar, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Bischoff
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D003470:Culture Media; D015964:Gene Expression Regulation, Bacterial; D006427:Hemin / Q000378:metabolism / Q000494:pharmacology*; D006460:Hemolysin Proteins / Q000235:genetics / Q000378:metabolism*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007501:Iron / Q000378:metabolism; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development / Q000472:pathogenicity*; D014157:Transcription Factors
chemical_list: D001426:Bacterial Proteins; D003470:Culture Media; D006460:Hemolysin Proteins; C433805:SaeR protein, Staphylococcus aureus; D014157:Transcription Factors; D006427:Hemin; D007501:Iron; D011494:Protein Kinases; C527351:SaeS protein, Staphylococcus aureus