Surface-associated M protein is a major virulence factor in Streptococcus p
yogenes which confers bacterial resistance to phagocytosis. However, many S
. pyogenes strains also express additional structurally related so-called M
-like proteins. The strain studied here is of the clinically important hll
serotype and expresses two structurally related surface proteins, the M1 pr
otein and protein H. Mutants were generated that expressed only one or none
of these proteins at the bacterial surface. For survival in human blood ei
ther protein H or M1 protein was sufficient, whereas the double mutant was
rapidly killed. The protein-binding properties of protein H, M1 protein, an
d the mutants suggest that bacterial binding of immunoglobulin G and factor
H or factor H-like protein 1, which are regulatory proteins in the complem
ent system, contribute to the antiphagocytic property.