Open AccessTrxR, a New CovR-Repressed Response Regulator That Activates the Mga Virulence Regulon in Group A Streptococcus
Author(s) -
Temekka V. Leday,
Kathryn M. Gold,
Traci L. Kinkel,
Samantha Roberts,
June R. Scott,
Kevin S. McIver
Publication year - 2008
Publication title -
infection and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.508
H-Index - 220
eISSN - 1070-6313
pISSN - 0019-9567
DOI - 10.1128/iai.00597-08
Subject(s) - virulence , regulon , biology , operon , complementation , mutant , microbiology and biotechnology , streptococcus pneumoniae , streptococcus pyogenes , repressor , pathogen , wild type , gene , transcription factor , genetics , bacteria , staphylococcus aureus , antibiotics
Coordinate regulation of virulence factors by the group A streptococcus (GAS)Streptococcus pyogenes is important in this pathogen's ability to cause disease. To further elucidate the regulatory network in this human pathogen, the CovR-repressed two-component system (TCS)trxSR was chosen for further analysis based on its homology to a virulence-related TCS inStreptococcus pneumoniae . In a murine skin infection model, an insertion mutation in the response regulator gene,trxR , led to a significant reduction in lesion size, lesion severity, and lethality. Curing thetrxR mutation restored virulence comparable to the wild-type strain. ThetrxSR operon was defined in vivo, and CovR was found to directly repress its promoter in vitro. DNA microarray analysis established that TrxR activates transcription of Mga-regulated virulence genes, which may explain the virulence attenuation of thetrxR mutant. This regulation appears to occur by activation of themga promoter, Pmga , as demonstrated by analysis of a luciferase reporter fusion. Complementation of thetrxR mutant withtrxR on a plasmid restored expression of Mga regulon genes and restored virulence in the mouse model to wild-type levels. TrxR is the first TCS shown to regulate Mga expression. Because it is CovR repressed, TrxR defines a new pathway by which CovR can influence Mga to affect pathogenesis in the GAS.