RNAIII-independent target gene control by the agr quorum-sensing system: insight into the evolution of virulence regulation in Staphylococcus aureus.
Cell-density-dependent gene regulation by quorum-sensing systems has a crucial function in bacterial physiology and pathogenesis. We demonstrate here that the Staphylococcus aureus agr quorum-sensing regulon is divided into (1) control of metabolism and PSM cytolysin genes, which occurs independently of the small regulatory RNA RNAIII, and (2) RNAIII-dependent control of additional virulence genes. Remarkably, PSM expression was regulated by direct binding of the AgrA response regulator. Our findings suggest that quorum-sensing regulation of PSMs was established before wide-ranging control of virulence was added to the agr regulon, which likely occurred by development of the RNAIII-encoding region around the gene encoding the PSM delta-toxin. Moreover, the agr regulon in the community-associated methicillin-resistant S. aureus MW2 considerably differed from that previously determined using laboratory strains. By establishing a two-level model of quorum-sensing target gene regulation in S. aureus, our study gives important insight into the evolution of virulence control in this leading human pathogen.
Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.
Shu Y
SY
Queck
Max
M
Jameson-Lee
Amer E
AE
Villaruz
Thanh-Huy L
TH
Bach
Burhan A
BA
Khan
Daniel E
DE
Sturdevant
Stacey M
SM
Ricklefs
Min
M
Li
Michael
M
Otto
D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D001427:Bacterial Toxins / Q000235:genetics; D001483:Base Sequence; D004269:DNA, Bacterial / Q000235:genetics; D019143:Evolution, Molecular; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D006801:Humans; D016106:Methicillin Resistance / Q000235:genetics; D008954:Models, Biological; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D053038:Quorum Sensing / Q000235:genetics / Q000502:physiology; D012329:RNA, Bacterial / Q000235:genetics*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D014774:Virulence / Q000235:genetics / Q000502:physiology
C095698:Agr protein, Staphylococcus aureus; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004269:DNA, Bacterial; D012329:RNA, Bacterial; C096035:RNAIII, Staphylococcus aureus; D015534:Trans-Activators