NUCLEOTIDE SUBSTITUTIONS AND SMALL-SCALE INSERTION PRODUCE SIZE AND ANTIGENIC VARIATION IN GROUP-A STREPTOCOCCAL M1-PROTEIN

The presence of M protein on the surface of group A streptococci (GAS) confers the ability of the cell to resist phagocytosis in the absence of type-specific antibodies. It undergoes antigenic variation with mo re than 80 different serotypes having been defined. We have sequenced the M protein gene (emm1.1) from strain CS190 and present evidence tha t individual nucleotide substitutions are responsible for sequence var iation in the N-terminal non-repeat region of emm1.1 and these substit utions have altered antibody recognition of opsonic epitopes. The N-te rminal non-repeat domains of two other closely related strains, 71-155 and 76-088, were found to have sequence identical to emml.1 with the addition of a 21 bp insert. This study provides the first evidence tha t nucleotide substitutions and small insertions are responsible for si ze and antigenic variation in the N-terminal non-repeat domain of the M protein of GAS.