title: Deferoxamine mesylate enhances virulence of community-associated methicillin resistant Staphylococcus aureus.
abstract: Staphylococcus aureus is a leading cause of bacterial infections. Strains of community-associated methicillin-resistant S. aureus (CA-MRSA), such as USA300, display enhanced virulence and fitness. Patients suffering from iron overload diseases often undergo iron chelation therapy with deferoxamine mesylate (DFO). Here, we show that USA300 uses this drug to acquire iron. We further demonstrate that mice administered DFO I.P., versus those not administered DFO, had significantly higher bacterial burden in livers and kidneys after I.V. challenge with USA300, associated with increased abscess formation and tissue destruction. The virulence of USA300 mutants defective for DFO uptake was not affected by DFO treatment.
authors.affiliation: Department of Microbiology & Immunology, University of Western Ontario, London N6A 5C1, Ontario, Canada.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Arifin
authors.affiliation: Department of Microbiology & Immunology, University of Western Ontario, London N6A 5C1, Ontario, Canada.
authors.forename: Mélissa
authors.initials: M
authors.lastname: Hannauer
authors.affiliation: Department of Animal Care and Veterinary Services, University of Western Ontario, London N6A 5C1, Ontario, Canada.
authors.forename: Ian
authors.initials: I
authors.lastname: Welch
authors.affiliation: Department of Microbiology & Immunology, University of Western Ontario, London N6A 5C1, Ontario, Canada; Centre for Human Immunology, University of Western Ontario, London N6A 5C1, Ontario, Canada. Electronic address: deh@uwo.ca.
authors.forename: David E
authors.initials: DE
authors.lastname: Heinrichs
mesh_terms: D000038:Abscess / Q000382:microbiology / Q000473:pathology; D000825:Animal Structures / Q000382:microbiology / Q000473:pathology; D000818:Animals; D058491:Bacterial Load; D003676:Deferoxamine / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D007501:Iron / Q000378:metabolism*; D007668:Kidney / Q000382:microbiology; D008099:Liver / Q000382:microbiology; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development* / Q000472:pathogenicity; D008807:Mice, Inbred BALB C; D017262:Siderophores / Q000378:metabolism*; D013203:Staphylococcal Infections / Q000382:microbiology / Q000473:pathology; D014774:Virulence / Q000187:drug effects
chemical_list: D017262:Siderophores; D007501:Iron; D003676:Deferoxamine
keywords: DFO; Iron; MRSA; Staphylococcus aureus; Virulence