Environmental regulation of virulence in group A streptococci: transcription of the gene encoding M protein is stimulated by carbon dioxide

Abstract

We have found that different atmospheres can have significant effects on the transcription of emm, the gene that encodes M protein, the major virulence factor of the group A streptococcus (Streptococcus pyogenes). Expression of emm was monitored by constructing a transcriptional fusion of the promoter for emm6.1 from S. pyogenes JRS4 to a promoterless chloramphenicol acetyltransferase gene. Transcription, as measured by determining chloramphenicol acetyltransferase specific activity, was stimulated by as much as 25-fold by increased carbon dioxide tension. Expression was greater in the latter stages of growth and was not affected by growth at 30 instead of 37 degrees C. Insertional inactivation of mry, a gene encoding a positive regulator of emm6.1, reduced chloramphenicol acetyltransferase activity below the detectable level. We conclude that expression of emm is influenced by environmental factors and that the level of carbon dioxide is one signal that may influence expression of M protein during infection.

Analysis of the Transcriptome of Group A Streptococcus in Mouse Soft Tissue Infection

“…Information about stage 1 is based on an expanding body of work, 8,10,11,34,103 and our results support this information by combined early expression of Mga, Ihk/Irr, and FasBCA/X regulatory systems that promote evasion of immune and innate host defenses and enhance host cell contact through surface adhesin production. Down-regulation of the negative regulatory systems of PerR, CovR/S, and CrgR promote production of reactive oxygen species detoxifying enzymes, hyaluronic acid capsule, and antimicrobial peptide resistance mechanisms, respectively, 8,35,[103][104][105][106][107] and our soft tissue model demonstrates similar results. Interestingly, we have discovered that transcription of transport and central metabolism genes appears tailored to unique GAS environments where host glycopeptides and complex carbohydrates are available, including maltodextrins, but which must be used under acidic and hypoxic conditions.…”

Regulation of bacterial virulence gene expression by the host environment.

“…O 2 concentrations vary greatly between the lumen of the bowel and perfused tissue, and low oxygen stimulates Salmonella invasion from the gastrointestinal tract. CO 2 concentration of tissues and the respiratory mucosa is elevated with respect to the normal atmospheric level, and CO 2 has been shown to regulate M-protein synthesis in streptococci (5). pH changes abruptly in the intestinal tract and regulates synthesis of acid stress proteins in bacteria exposed to gastric contents or signals localization in the small bowel by the increase in pH.…”

Adherence and Biofilm Production of Streptococcus pyogenes

“…Similarly as in protein F1/SfbI, F2 activity is also response to the environmental oxygen pressure [13]. Unlike these two proteins, M protein expression is enhanced in the deeper tissues with increased pressure of carbon dioxide, preventing phagocytosis and contributing to the dissemination of GAS [14].…”