Absence of SpeB production in virulent large capsular forms of group A streptococcal strain 64

Passage in human blood of group A streptococcal isolate 64p was previously shown to result in the enhanced expression of M and M-related proteins. Sim ilarly, when this isolate was injected into mice via an air sec model for s kin infection, organisms recovered from the spleens showed both increased e xpression of hi and M-related proteins and increased skin-invasive potentia l. We show that these phenotypic changes were not solely the result of incr eased transcription of the mRNAs encoding the M and M-related gene products . Rather, the altered expression was associated with posttranslational modi fications of the M and M-related proteins that occur in this strain, based on the presence or absence of another virulence protein, the streptococcal cysteine protease SpeB. The phenotypic variability also correlates with col ony size variation. Large colonies selected by both regimens expressed more hyaluronic acid, which may explain differences in colony morphology. All l arge-colony variants were SpeB negative and expressed three distinct immuno globulin G (IgG)-binding proteins in the M and M-related protein family. Sm all-colony variants were SpeB positive and bound little Ige through their M and M-related proteins because these proteins, although made, were degrade d or altered in profile by the SpeB protease, We conclude that passage in e ither human blood or a mouse selects for a stable, phase-varied strain of g roup A streptococci which is altered in many virulence properties.