A role for the fibrinogen-binding regions of streptococcal M proteins in phagocytosis resistance

All virulent group A streptococcal isolates bind fibrinogen, a property tha t is closely linked to expression of type-specific antiphagocytic surface m olecules designated M proteins. Here we show that although the M proteins f rom two different strains, M1 and M5, both bind fibrinogen with high affini ty, they interact with different regions in the ligand. Moreover, mapping e xperiments demonstrated that the fibrinogen-binding regions in the M1 and M 5 proteins are quite dissimilar at the amino acid sequence level and that t hey bind to different regions in the plasma protein. In spite of these diff erences, the fibrinogen-binding regions of M1 and M5 could both be shown to contribute to streptococcal survival in human blood, providing evidence fo r the distinct function of a plasma protein interaction in bacterial pathog enesis.