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Background  Alpha-hemolysin (Hla) is a major virulence factor in the pathogenesis of  Staphylococcus aureus  infection, being active against a wide range of host cells. Although  hla  is ubiquitous in  S. aureus , its genetic diversity and variation in expression in different genetic backgrounds is not known. We evaluated nucleotide sequence variation and gene expression profiles of  hla  among representatives of hospital (HA) and community-associated (CA)  S. aureus  clones.    Methods  51 methicillin-resistant  S. aureus  and 22 methicillin-susceptible  S. aureus  were characterized by PFGE,  spa  typing, MLST and SCC mec  typing. The internal regions of  hla  and the  hla  promoter were sequenced and gene expression was assessed by RT-PCR.    Results  Alpha-hemolysin encoding- and promoter sequences were diverse, with 12 and 23 different alleles, respectively. Based on phylogenetic analysis, we suggest that  hla  may have evolved together with the  S. aureus  genetic background, except for ST22, ST121, ST59 and ST93. Conversely, the promoter region showed lack of co-evolution with the genetic backgrounds. Four non-synonymous amino acid changes were identified close to important regions of  hla  activity. Amino acid changes in the RNAIII binding site were not associated to  hla  expression. Although expression rates of  hla  were in general strain-specific, we observed CA clones showed significantly higher  hla  expression (p = 0.003) when compared with HA clones.    Conclusion  We propose that the  hla  gene has evolved together with the genetic background. Overall, CA genetic backgrounds showed higher levels of  hla  expression than HA, and a high strain-to-strain variation of gene expression was detected in closely related strains.

Insights into Alpha-Hemolysin (Hla) Evolution and Expression among Staphylococcus aureus Clones with Hospital and Community Origin