A SECRETED STREPTOCOCCAL CYSTEINE PROTEASE CAN CLEAVE A SURFACE-EXPRESSED M1 PROTEIN AND ALTER THE IMMUNOGLOBULIN BINDING-PROPERTIES

Previous studies of recent clinical isolates of serotype M1 group A st reptococci indicated that they display two patterns of non-immune huma n IgG subclass binding reactivity associated with their hill protein. One group reacted with all four IgG subclasses (type IIo), while the s econd group expressed an M1 protein reacting preferentially with human IgG, (type IIb). In this study, we have demonstrated that a cysteine protease, SpeB, present in culture supernatants of M1 serotype group A streptococcal isolates expressing type IIb IgG binding protein, can c onvert a recombinant Emm1 protein from a type IIo functional profile t o a type IIb profile by removal of 24 amino acids from the hi-terminus of the mature M1 protein. Furthermore, SpeB can convert bacteria expr essing IgG binding proteins of the type Ilo phenotype into those expre ssing type IIb proteins. The role of the cysteine protease as the cent ral bacterial enzyme in this posttranslational modification event was confirmed by generation of an isogenic SpeB-negative mutant.