To begin to examine the streptolysins during acute S. pyogenes infections, genetic deletions of the slo operon, including the slo, ifs and nga genes [27], or the sag operon encoding SLS biosynthesis and secretion [23], were generated in S. pyogenes strain MGAS8232 (Fig 1A and 1B), which was isolated from a patient with acute rheumatic fever [28]. This evidence concerns the gene SAG and rheumatic fever.