Prevention and treatment strategies targeting α-hemolysin (Hla) of Staphylococcus aureus

Abstract:

The emergence of superbugs with both high pathogenicity and high antimicrobial resistance poses a major challenge to public health. In Staphylococcus aureus, α-hemolysin (Hla) is a key virulence factor mediating infection and thus represents a crucial target for prevention and control. This review first summarized the structural characteristics of Hla in its monomeric crystalline form and heptameric pore assembly. It then systematically delineated the multi-layered and fine-tuned regulation of Hla expression, involving the hla gene locus, the Agr quorum-sensing system, the Sar protein family, the Staphylococcal accessory element regulator (SaeRS) two-component system, and other auxiliary regulators. The pathogenic mechanisms of Hla were further elaborated from the perspectives of both cellular effects and host receptors. Finally, this review summarized recent advances in prevention and treatment strategies targeting Hla, including vaccines, monoclonal antibodies, natural compounds, and nanoparticles, offering new insights and candidate approaches for the precise prevention of drug-resistant S. aureus infections.