Group A streptococcal phagocytosis resistance is independent of complementfactor H and factor H-like protein 1 binding

Factor H (FH) and factor H-like protein 1 (FHL-1) regulate complement activ ation through the alternative pathway. Several extracellular bacterial path ogens, prime targets for the complement system, bind FH and FHL-1, thereby acquiring a potential mechanism for minimizing complement deposition on the ir surface. For group A streptococci (GAS), surface-bound antiphagocytic M proteins mediate the interaction. To study the role of the FH-FHL-1 interac tion for complement deposition and opsonophagocytosis of GAS, we first cons tructed a set of truncated M5 protein variants and expressed them on the su rface of a homologous M-negative GAS strain. Binding experiments with the r esulting strains demonstrate that the major FH-FHL-1 binding is located in a 42-amino-acid region within the N-terminal third of M5. Measurement of ba cteria-bound complement factor C3 after incubation in plasma showed that th e presence of this region had little impact upon complement deposition thro ugh the alternative pathway. Moreover, streptococci expressing M5 proteins lacking the major FH and FHL-1 binding sequence resisted phagocytosis in hu man blood as efficiently as bacteria expressing the wild-type protein. Cons equently, the data suggest that the binding of the regulators of the altern ative pathway is of limited importance for GAS phagocytosis resistance.