Transcriptional analysis of mga, a regulatory gene in Streptococcus pyogenes: identification of monocistronic and bicistronic transcripts that phase vary

Transcription of several surface virulence proteins of Streptococcus pyogenes is regulated by Mga, a protein that shows homology to response regulators of two-component signal-transducing systems. Two of these surface virulence proteins, M protein and C5a peptidase, undergo phase variation. To determine whether Mga itself undergoes phase variation and might allow the phasing switch to coordinate the activity of these genes, expression of the mga gene was analyzed. We show for the first time that there are two mga-specific transcripts: a 3.8-kb bicistronic message that includes both mga and emm12 genes and a monocistronic 1.6-kb mga message. Both transcripts phase vary and are present in higher amounts in M⁺ variants than in M⁻ variants. Incubation of RNA with rifampicin indicates that the smaller 1.6-kb message is not a processed product. Two promoters were mapped upstream of mga: P1 at position 666 (−395) and P2 at position 978 (−83). In strain CS46 (Δmga), transcription initiation from the P1 promoter does not occur, and multiple start sites are found around the P2 promoter. Complementation experiments indicate that sequences upstream of the P2 promoter are required for activation of emm12 and scpA by Mga in trans.