Expression of different group A streptococcal M proteins in an isogenic background demonstrates diversity in adherence to and invasion of eukaryotic cells

The M protein of group A streptococcus (GAS) is considered to be a major vi rulence factor because it renders GAS resistant to phagocytosis and allows bacterial growth in human blood. There are more than 80 known serotypes of M proteins, and protective opsonic antibodies produced during disease in hu mans are serotype specific. M proteins also mediate bacterial adherence to epithelial cells of skin and pharynx. GAS strains vary in the genomic organ ization of the mga regulon, which contains the genes encoding M and M-like proteins and other virulence factors. This diversity of organization makes it difficult to assess virulence of M proteins of different serotypes, unle ss they can be expressed in an isogenic background. Here, we express M prot eins of different serotypes in the M protein- and protein F1-deficient GAS strain, SAMP, which also lacks M-like proteins, Genes encoding M proteins o f different serotypes (emmXs) have been integrated into the SAM2 chromosome in frame with the emm6.1 promoter and its mga regulon, resulting in simila r levels of emmX expression. Although SAMS exhibits a very low level of adh erence to and invasion of HEp-2 and HaCaT cells, a SAMS-derived strain expr essing M6 protein adheres to and invades both cell types, In contrast, the isogenic strain expressing M18 protein adheres to both cell types, but inva des with a very low efficiency. A strain expressing M3 protein adheres to b oth types of cells, but its invasion of HEp-2 cells is serum dependent. A G AS strain expressing M6 protein does not compete with the isogenic strain e xpressing M18 protein for adherence to or invasion of HaCaT cells. We concl ude that M proteins of different serotypes recognize different repertoires of receptors on the surfaces of eukaryotic cells.