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Staphylococcus aureus gamma-hemolysin AB (HlgAB) is a bicomponent pore-forming toxin composed of the class S component HlgA and the class F component HlgB, which together assemble into hetero-oligomeric β-barrel pores (such as 3A3B or 4A4B) on target cell membranes.[1][2][7] These water-soluble monomers bind to specific receptors like chemokine receptors CXCR1, CXCR2, and CCR2 on host cells, particularly neutrophils and other phagocytes, leading to cation-selective pore formation that disrupts membrane integrity, causes cell lysis, and contributes to immune evasion.[2][5] HlgAB exhibits hemolytic and leukotoxic activities, distinguishing it from related toxins like α-hemolysin by its selectivity for cations and hetero-oligomeric structure.[1][6] The genes encoding HlgA and HlgB are present in nearly all human S. aureus isolates (>99.5%), with high expression during growth in blood or phagocytosis, making HlgAB a major secreted virulence factor in staphylococcal infections.[5] In disease, it promotes tissue damage and systemic spread in conditions like catheter-related infections, pneumonia, and endocarditis by targeting immune cells.[3][5] No approved drugs directly target HlgAB, as it functions as a bacterial toxin rather than a host therapeutic receptor or enzyme.[1-12]
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