title: Rgg influences the expression of multiple regulatory loci to coregulate virulence factor expression in Streptococcus pyogenes.
abstract: The human pathogen Streptococcus pyogenes secretes many proteins to the cell wall and extracellular environment that contribute to virulence. Rgg regulates the expression of several exoproteins including a cysteine protease (SPE B), a nuclease (MF-1), a putative nuclease (MF-3), and autolysin. The functional heterogeneity of Rgg-regulated exoproteins and the lack of a conserved regulatory motif in the promoter regions of the genes suggested that Rgg interacts with additional regulatory networks to influence gene expression. DNA microarrays were used to test this hypothesis by comparing genomewide transcript profiles of S. pyogenes NZ131 and isogenic derivative NZ131 rgg during the exponential phase of growth. Transcripts of known and putative virulence-associated genes were more abundant in the rgg mutant, including emm, scpA, orfX, scl1, hasAB, slo, sagA, ska, speH, grab, mac, mf-1, and mf-3. Increased transcription of emm, scpA, and orfX in the rgg mutant was associated with increased production of the corresponding proteins. Differences in the expression of virulence-associated genes were associated with changes in the expression of several regulatory genes, including mga, sagA, csrRS, and fasBCA. The results show that Rgg influences the expression of multiple regulatory networks to coregulate virulence factor expression in S. pyogenes.
authors.affiliation: Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840, USA. mchausse@usd.edu
authors.forename: Michael S
authors.initials: MS
authors.lastname: Chaussee
authors.forename: Gail L
authors.initials: GL
authors.lastname: Sylva
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Sturdevant
authors.forename: Laura M
authors.initials: LM
authors.lastname: Smoot
authors.forename: Morag R
authors.initials: MR
authors.lastname: Graham
authors.forename: Robert O
authors.initials: RO
authors.lastname: Watson
authors.forename: James M
authors.initials: JM
authors.lastname: Musser
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D006801:Humans; D016296:Mutagenesis; D011494:Protein Kinases / Q000235:genetics; D018085:Regulon; D012097:Repressor Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013297:Streptococcus pyogenes / Q000235:genetics* / Q000472:pathogenicity; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; C432143:CsrR protein, Streptococcus pyogenes; D004268:DNA-Binding Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C068267:mry protein, Streptococcus pyogenes; C074779:rgg protein, Streptococcus; D011494:Protein Kinases; C432144:CsrS protein, bacteria