title: Identifying potential therapeutic targets of methicillin-resistant Staphylococcus aureus through in vivo proteomic analysis.
abstract: BACKGROUND
  Detailed knowledge on protein repertoire of a pathogen during host infection is needed for both developing a better understanding of the pathogenesis and defining potential therapeutic targets. Such data, however, have been missing for Staphylococcus aureus, a major human pathogen.
  
  
  METHODS
  We determined the surface proteome of methicillin-resistant S. aureus (MRSA) clone usa300 derived directly from murine systemic infectiON.
  
  
  RESULTS
  The majority of the in vivo-expressed surface-associated proteins were lipoproteins involved in nutrient acquisition, especially uptake of metal ions. Enzyme-linked immunosorbent assay (ELISA) of convalescent human serum samples revealed that proteins that were highly produced during murine experimental infection were also produced during natural human infection. We found that among the 7 highly abundant lipoproteins only MntC, which is the manganese-binding protein of the MntABC system, was essential for MRSA virulence during murine systemic infection. Moreover, we show that MntA and MntB are equally important for MRSA virulence.
  
  
  CONCLUSIONS
  Besides providing experimental evidence that MntABC might be a potential therapeutic target for the development of antibiotics, our in vivo proteomics data will serve as a valuable basis for defining potential antigen combinations for multicomponent vaccines.
authors.affiliation: Department of Medicine, University of California, San Francisco.
authors.forename: Binh An
authors.initials: BA
authors.lastname: Diep
authors.forename: Qui
authors.initials: Q
authors.lastname: Phung
authors.forename: Shailesh
authors.initials: S
authors.lastname: Date
authors.forename: David
authors.initials: D
authors.lastname: Arnott
authors.forename: Corey
authors.initials: C
authors.lastname: Bakalarski
authors.forename: Min
authors.initials: M
authors.lastname: Xu
authors.forename: Gerald
authors.initials: G
authors.lastname: Nakamura
authors.forename: Danielle L
authors.initials: DL
authors.lastname: Swem
authors.forename: Mary Kate
authors.initials: MK
authors.lastname: Alexander
authors.forename: Hoan N
authors.initials: HN
authors.lastname: Le
authors.forename: Thuy T
authors.initials: TT
authors.lastname: Mai
authors.forename: Man-Wah
authors.initials: MW
authors.lastname: Tan
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Brown
authors.forename: Mireille
authors.initials: M
authors.lastname: Nishiyama
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D006801:Humans; D007668:Kidney / Q000382:microbiology; D008074:Lipoproteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000378:metabolism* / Q000472:pathogenicity; D051379:Mice; D040901:Proteomics; D044967:Serum / Q000276:immunology; D013203:Staphylococcal Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D013209:Staphylococcal Vaccines / Q000276:immunology; D014774:Virulence
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D008074:Lipoproteins; D008565:Membrane Proteins; D013209:Staphylococcal Vaccines
keywords: MRSA; Staphylococcus aureus; bacterial pathogenesis; proteomics; vaccine and antibiotic development