Expression of γ-hemolysin regulated by sae in Staphylococcus aureus strain Smith 5R

Staphylococcus aureus strain Smith 5R produces a two-component pore-forming toxin and forms a rough-surfaced colony with hemolytic haloes on human red blood cell plates (R[+]). Serial subcultures of the strain in broth caused the appearance of γ-hemolysin negative variants with a smooth colony shape (S[-]), and the S[-] valiant became predominant in culture. The R[+] strain, in which agrA is naturally disrupted by an insertion of IS1181, produced high levels of γ-hemolysin. In the S[-] variant, expression of both hlg and lukS-F mRNAs was strongly reduced. Nucleotide sequencing of the sae locus revealed that all isolated S[-] variants had spontaneous mutations in the sae locus. Recovery of γ-hemolysin productivity in S[-] by transformation of the wild-type sae allele strongly suggested that the expression of γ-hemolysin is positively regulated by sae in an agr-independent manner.