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Leukocidin ED (LukED) is a bicomponent pore-forming toxin secreted by Staphylococcus aureus, consisting of LukE (S-class subunit) and LukD (F-class subunit), which assemble into beta-barrel pores that lyse target host cells. LukE binds specific chemokine receptors such as ACKR1 (DARC/Duffy antigen), CCR2, CCR5, CXCR1, and CXCR2 on human erythrocytes, leukocytes, neutrophils, macrophages, dendritic cells, and T cells, enabling cell-specific targeting and membrane damage. This toxin uniquely kills murine neutrophils and phagocytes in vivo, promoting S. aureus replication during bloodstream infections by eliminating immune cells recruited to infection sites like kidneys. LukED contributes critically to S. aureus virulence in bacteremia and systemic infections, including methicillin-resistant strains (MRSA), and is conserved across S. aureus isolates. Crystal structures of LukE (PDB: 3ROH, 7P93) and LukD reveal conserved domains (cap, rim, stem) with receptor-binding sites involving sulfotyrosine motifs, highlighting potential for therapeutic inhibition. No approved drugs target LukED, but its role positions it as a candidate for novel antibiotics against S. aureus infections.
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