title: Nasal carriage as a source of agr-defective Staphylococcus aureus bacteremia.
abstract: Inactivating mutations in the Staphylococcus aureus virulence regulator agr are associated with worse outcomes in bacteremic patients. However, whether agr dysfunction is primarily a cause or a consequence of early bacteremia is unknown. Analysis of 158 paired S. aureus clones from blood and nasal carriage sites in individual patients revealed that recovery of an agr-defective mutant from blood was usually predicted by the agr functionality of carriage isolates. Many agr-positive blood isolates produced low levels of hemolytic toxins, but levels were similar to those of colonizing strains within patients, suggesting that introduction into the blood did not select for mutations with minor functional effects. Evidently, the transition from commensalism to opportunism in S. aureus does not require full virulence in hospitalized patients. Furthermore, agr-defective mutants were found in uninfected nasal carriers in the same proportion as in carriers who develop bacteremia, suggesting low correlation between virulence and infectivity.
authors.affiliation: Skirball Institute of Biomolecular Medicine, and Departments of Medicine and Microbiology, New York University School of Medicine, New York, USA.
authors.forename: Davida S
authors.initials: DS
authors.lastname: Smyth
authors.forename: Jared M
authors.initials: JM
authors.lastname: Kafer
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Wasserman
authors.forename: Lili
authors.initials: L
authors.lastname: Velickovic
authors.forename: Barun
authors.initials: B
authors.lastname: Mathema
authors.forename: Robert S
authors.initials: RS
authors.lastname: Holzman
authors.forename: Tiffany A
authors.initials: TA
authors.lastname: Knipe
authors.forename: Karsten
authors.initials: K
authors.lastname: Becker
authors.forename: Christof
authors.initials: C
authors.lastname: von Eiff
authors.forename: Georg
authors.initials: G
authors.lastname: Peters
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.forename: Barry N
authors.initials: BN
authors.lastname: Kreiswirth
authors.forename: Richard P
authors.initials: RP
authors.lastname: Novick
authors.forename: Bo
authors.initials: B
authors.lastname: Shopsin
mesh_terms: D016470:Bacteremia / Q000382:microbiology*; D001426:Bacterial Proteins / Q000145:classification / Q000235:genetics; D002353:Carrier State / Q000382:microbiology*; D005838:Genotype; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000235:genetics* / Q000302:isolation & purification; D058889:Molecular Typing; D009297:Nasal Mucosa / Q000382:microbiology; D017422:Sequence Analysis, DNA; D013203:Staphylococcal Infections / Q000382:microbiology*; D015534:Trans-Activators / Q000145:classification / Q000172:deficiency* / Q000235:genetics; D014774:Virulence
chemical_list: C095698:Agr protein, Staphylococcus aureus; D001426:Bacterial Proteins; D015534:Trans-Activators