title: Inactivation of the group A Streptococcus regulator srv results in chromosome wide reduction of transcript levels, and changes in extracellular levels of Sic and SpeB.
abstract: Group A Streptococcus is characterized by the ability to cause a diverse number of human infections including pharyngitis, necrotizing fasciitis, toxic shock syndrome, and acute rheumatic fever, yet the regulation of streptococcal genes involved in disease processes and survival in the host is not completely understood. Genome scale analysis has revealed a complex regulatory network including 13 two-component regulatory systems and more than 100 additional putative regulators, the majority of which remain uncharacterized. Among these is the streptococcal regulator of virulence, Srv, the first Group A Streptococcus member of the Crp/Fnr family of transcriptional regulators. Previous work demonstrated that the loss of srv resulted in a significant decrease in Group A Streptococcus virulence. To begin to define the gene products influenced by Srv, we combined microarray and two-dimensional gel electrophoresis analysis. Loss of srv results in a chromosome wide reduction of gene transcription and changes in the production of the extracellular virulence factors Sic (streptococcal inhibitor of complement) and SpeB (cysteine proteinase). Sic levels are reduced in the srv mutant, whereas the extracellular concentration and activity of SpeB is increased. These data link Srv to the increasingly complex GAS regulatory network.
authors.affiliation: Department of Microbiology and Immunology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA. sreid@wfubmc.edu
authors.forename: Sean D
authors.initials: SD
authors.lastname: Reid
authors.forename: Michael S
authors.initials: MS
authors.lastname: Chaussee
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Doern
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Chaussee
authors.forename: Alison G
authors.initials: AG
authors.lastname: Montgomery
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Sturdevant
authors.forename: James M
authors.initials: JM
authors.lastname: Musser
mesh_terms: D000942:Antigens, Bacterial / Q000378:metabolism; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D001426:Bacterial Proteins / Q000096:biosynthesis* / Q000235:genetics; D002352:Carrier Proteins / Q000378:metabolism; D002364:Caseins / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000096:biosynthesis* / Q000235:genetics; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D015964:Gene Expression Regulation, Bacterial; D020868:Gene Silencing; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D013290:Streptococcal Infections / Q000382:microbiology; D013297:Streptococcus pyogenes / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D014158:Transcription, Genetic / Q000235:genetics; D014774:Virulence
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D002364:Caseins; C097739:SIC protein, Streptococcus; C014689:streptococcal M protein; D003546:Cysteine Endopeptidases; C042477:streptopain