The importance of SLO in the biology and pathogenesis of GAS infection is supported by the nearly universal production of SLO by clinical isolates, attenuation of SLO-deficient mutants in experimental infection models, and the molecular epidemiological observation that invasive clones of GAS that have emerged during and since the 1980s exhibit genomic evidence of acquisition of a highly active promoter driving increased expression of the operon encoding SLO and NADase (17, 18). This evidence concerns the gene KCNMA1 and infection.