Impact of the Streptococcus pyogenes Mga regulator on human matrix protein binding and interaction with eukaryotic...

The Streptococcus pyogenes (group A streptococci, GAS) stand-alone Mga regulator has been shown to positively control surface-expressed virulence factors like the antiphagocytic M protein during exponential growth phase and thus, was implicated to contribute to the acute infection process. In the present study, we generated mga mutants as well as mga promoter - luciferase reporter fusions in weakly and strongly encapsulated serotype M2 and M49 GAS strains. Employing the luc reporter fusions, we showed that the complex growth medium THY-broth decreased mga expression and identified albumin as one component responsible for this effect. Fibrinogen and cU50980omponents of the complex DMEM cell culture medium induced the mga transcription rate. The attachment of mga mutants to immobilized human matrix proteins (collagen type I, fibronectin, keratin, laminin) and serum proteins (albumin, fibrinogen) was consistently reduced. Changing the Mn(2+) or Ca(2+) growth medium concentrations did not affect the fibronectin/collagen binding of M49 GAS wild-type and mga mutant strains. Medium supplementation with the oxidative stressor paraquat or anaerobic growth on THY-agar led to a relatively increased human matrix protein binding of the mga mutant. Opposite to their matrix protein-binding behaviour, the M2 and M49 mga mutants displayed an increased attachment and internalization rate for eukaryotic cells. The host cell viability was considerably reduced after prolonged exposure to mga mutants. By generating and testing corresponding M protein gene (emm) mutants, features of the eukaryotic cell interaction could not be associated to the Mga - M protein regulatory axis. In conclusion, the present results support the postulated central role of Mga regulation for GAS host colonization and acute infection stages.