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

• Published in: FEMS immunology and medical microbiology 2006-11, Vol.48 (2), p.283-292
• Main Authors: Reid, Sean D., Chaussee, Michael S., Doern, Christopher D., Chaussee, Michelle A., Montgomery, Alison G., Sturdevant, Daniel E., Musser, James M.
• Format: Article
• Language: English
• Subjects: Antigens, Bacterial - metabolism; Bacterial Outer Membrane Proteins - metabolism; Bacterial Proteins - biosynthesis; Bacterial Proteins - genetics; Bacteriology; Biological and medical sciences; Carrier Proteins - metabolism; Caseins - metabolism; Chromosomes; Cysteine Endopeptidases - biosynthesis; Cysteine Endopeptidases - genetics; Cysteine proteinase; Deactivation; DNA microarrays; Electrophoresis; Electrophoresis, Gel, Two-Dimensional - methods; Extracellular levels; Fasciitis; Fundamental and applied biological sciences. Psychology; Gel electrophoresis; Gene expression; Gene Expression Regulation, Bacterial; Gene regulation; Gene Silencing; Genomes; group A Streptococcus; Inactivation; Microbiology; Miscellaneous; Necrotizing fasciitis; Oligonucleotide Array Sequence Analysis - methods; Pharyngitis; Proteinase; Reduction; Rheumatic fever; Septic shock; Srv; Streptococcal Infections - microbiology; streptococcal regulator of virulence; Streptococcus; Streptococcus infections; Streptococcus pyogenes; Streptococcus pyogenes - genetics; Streptococcus pyogenes - metabolism; Streptococcus pyogenes - pathogenicity; Toxic shock syndrome; Transcription; Transcription, Genetic - genetics; Two dimensional analysis; Virulence; Virulence factors; virulence gene regulation
• ISSN: 0928-8244; 1574-695X; 2049-632X
• DOI: 10.1111/j.1574-695X.2006.00150.x

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.