Background: Numerous regulatory systems of Group A streptococcus (GAS) allow adaption to various host environments, enabling infections in diverse human tissues. Mga (multiple gene activator) regulates transcription of up to 10% of the GAS genome, particularly during acute phases of infection. The core Mga regulon contains genes encoding proteins involved in adhesion and evasion of immune responses including the M protein and the M-like proteins Mrp and Enn.
Methods: The genetic make-up of the core Mga regulon of GAS was characterised utilising a collection of over 1400 GAS genomes containing 132 emm-types and 42 emm-clusters, collected from multiple continents and various clinical manifestations. Precise annotation of all core Mga genes has been undertaken and sequence variations were examined with MUSCLE alignments.
Results: In 89% of genomes the locus contained genes mga, mrp, emm, enn and scpa encoding Mga, Mrp, M, Enn and C5a peptidase proteins respectively, in the stated order. Only 8.6% of genomes had emm but neither mrp nor enn genes, and 58% of these also contained a gene for Sic or Protein H. The average pairwise identity within Enn and Mrp proteins was 70% and 81.2% respectively, which is much higher than within M proteins (52.6%).
Conclusions: The Mga regulon in most GAS strains encodes Mrp, M and Enn proteins, suggesting a paradigm shift from M-centric to more inclusive studies. The role of these M-like proteins should therefore be investigated in more details including the regulation of their expression together with their vaccine potential.