Variable susceptibility to opsonophagocytosis of group A streptococcus M-1 strains by human immune sera.

Immunity to group A streptococci (GAS) is thought to be related to the acquisition of type-specific antibody directed against the M protein. However, recent work suggests that immunity may only be strain and not M-type specific. Therefore, susceptibility of 70 different GAS M-1 strains to opsonization and killing by convalescent sera was compared by using a highly sensitive chemiluminescence assay and by standard bactericidal assay. Sequencing of the emm1 gene in 10 strains with variable susceptibility to opsonization revealed 100% homology in 9 strains. Several substitutions in the N-terminal and 2 in the A3 repeat regions of strain CS-190 were associated with profound resistance to opsonization. Thus amino acid substitutions within different regions of the M-1 protein molecule may adversely affect opsonization by immune sera. In addition, non-M protein factors from identical M types influence susceptibility to phagocytosis. These findings may in part explain the persistently high prevalence of M-1 strains worldwide over the last 15 years.