title: Role of the accessory gene regulator agr in community-associated methicillin-resistant Staphylococcus aureus pathogenesis.
abstract: The molecular basis underlying the pathogenic success of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is not completely understood, but differential gene expression has been suggested to account at least in part for the high virulence of CA-MRSA strains. Here, we show that the agr gene regulatory system has a crucial role in the development of skin infections in the most prevalent CA-MRSA strain USA300. Importantly, our data indicate that this is due to discrepancies between the agr regulon of CA-MRSA and those of hospital-associated MRSA and laboratory strains. In particular, agr regulation in strain USA300 led to exceptionally strong expression of toxins and exoenzymes, upregulation of fibrinogen-binding proteins, increased capacity to bind fibrinogen, and increased expression of methicillin resistance genes. Our findings demonstrate that agr functionality is critical for CA-MRSA disease and indicate that an adaptation of the agr regulon contributed to the evolution of highly pathogenic CA-MRSA.
authors.affiliation: Laboratory of Human Bacterial Pathogenesis, NIAID, NIH, Bldg. 33, 1W10, 9000 Rockville Pike, Bethesda, MD 20892, USA.
authors.forename: Gordon Y C
authors.initials: GY
authors.lastname: Cheung
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.forename: Burhan A
authors.initials: BA
authors.lastname: Khan
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Sturdevant
authors.forename: Michael
authors.initials: M
authors.lastname: Otto
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics*; D017714:Community-Acquired Infections / Q000235:genetics; D015870:Gene Expression; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics*; D016106:Methicillin Resistance / Q000235:genetics; D055624:Methicillin-Resistant Staphylococcus aureus / Q000235:genetics* / Q000472:pathogenicity; D051379:Mice; D008819:Mice, Nude; D020411:Oligonucleotide Array Sequence Analysis; D018085:Regulon / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013207:Staphylococcal Skin Infections / Q000235:genetics* / Q000276:immunology; D015534:Trans-Activators / Q000235:genetics*; D014774:Virulence
chemical_list: C095698:Agr protein, Staphylococcus aureus; D001426:Bacterial Proteins; D015534:Trans-Activators