title: Allele-dependent differences in quorum-sensing dynamics result in variant expression of virulence genes in Staphylococcus aureus.
abstract: Agr is an autoinducing, quorum-sensing system that functions in many Gram-positive species and is best characterized in the pathogen Staphylococcus aureus, in which it is a global regulator of virulence gene expression. Allelic variations in the agr genes have resulted in the emergence of four quorum-sensing specificity groups in S. aureus, which correlate with different strain pathotypes. The basis for these predilections is unclear but is hypothesized to involve the phenomenon of quorum-sensing interference between strains of different agr groups, which may drive S. aureus strain isolation and divergence. Whether properties intrinsic to each agr allele directly influence virulence phenotypes within S. aureus is unknown. In this study, we examined group-specific differences in agr autoinduction and virulence gene regulation by utilizing congenic strains, each harboring a unique S. aureus agr allele, enabling a dissection of agr locus-dependent versus genotype-dependent effects on quorum-sensing dynamics and virulence factor production. Employing a reporter fusion to the principal agr promoter, P3, we observed allele-dependent differences in the timing and magnitude of agr activation. These differences were mediated by polymorphisms within the agrBDCA genes and translated to significant variations in the expression of a key transcriptional regulator, Rot, and of several important exoproteins and surface factors involved in pathogenesis. This work uncovers the contribution of divergent quorum-sensing alleles to variant expression of virulence determinants within a bacterial species.
authors.affiliation: Molecular Pathogenesis Program and Departments of Microbiology and Medicine, the Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Geisinger
authors.forename: John
authors.initials: J
authors.lastname: Chen
authors.forename: Richard P
authors.initials: RP
authors.lastname: Novick
mesh_terms: D000483:Alleles; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D008969:Molecular Sequence Data; D053038:Quorum Sensing; D013045:Species Specificity; D013211:Staphylococcus aureus / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D037521:Virulence Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: C095698:Agr protein, Staphylococcus aureus; D001426:Bacterial Proteins; D015534:Trans-Activators; D037521:Virulence Factors