Affiliation:
1. 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, New York, USA
Abstract
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.
Publisher
American Society for Microbiology
Subject
Molecular Biology,Microbiology
Cited by
53 articles.
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