Distribution of streptococcal inhibitor of complement variants in pharyngitis and invasive isolates in an epidemic of serotype M1 group a Streptococcus infection

Streptococcal inhibitor of complement (Sic) is a highly polymorphic extrace llular protein made predominantly by serotype M1 group A Streptococcus (GAS ). New variants of the Sic protein frequently appear in M1 epidemics as a r esult of positive natural selection. To gain further understanding of the m olecular basis of M1 epidemics, the sic gene was sequenced from 471 pharyng itis and 127 pyogenic and blood isolates recovered from 598 patients living in metropolitan Helsinki, Finland, during a 37-month population-based surv eillance study. Most M1 GAS subclones recovered from pyogenic infections an d blood were abundantly represented in the pool of subclones causing pharyn gitis. Alleles shared among the pharyngitis, pyogenic, and blood samples we re identified in throat isolates a mean of 9.8 months before their recovery from pyogenic infections and blood, which indicates that selection of most sic variants occurs on mucosal surfaces. In contrast, no variation was ide ntified in the emm and covR/covS genes.