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 extracellular protein made predominantly by serotype M1 group A Streptococcus (GAS). New variants of the Sic protein frequently appear in M1 epidemics as a result of positive natural selection. To gain further understanding of the molecular basis of M1 epidemics, the sic gene was sequenced from 471 pharyngitis and 127 pyogenic and blood isolates recovered from 598 patients living in metropolitan Helsinki, Finland, during a 37-month population-based surveillance study. Most M1 GAS subclones recovered from pyogenic infections and blood were abundantly represented in the pool of subclones causing pharyngitis. Alleles shared among the pharyngitis, pyogenic, and blood samples were 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 identified in the emm and covR/covS genes. Although insight has been obtained about the microbial and host factors that contribute to epidemic waves of some pathogens, for most organisms molecular explanations for changes in disease frequency and severity are poorly understood. Molecular explanation of these phenomena is critical to the development of rational methods to limit pathogen emergence, resurgence, and dissemination. Group A Streptococcus (GAS) is a gram-positive human pathogen that causes pharyngitis (“strep throat”), invasive infections such as sepsis and necrotizing fasciitis, and postinfection sequelae that include rheumatic heart disease and glomerulonephritis. GAS is genetically highly heterogeneous. For example, 1100 distinct serotypes have been identified on the basis of antigenic differences in the M protein, an antiphago