The Staphylococcus aureus superantigen SElX is a bifunctional toxin that inhibits neutrophil function

Bacterial superantigens (sags) cause vβ-dependent t-cell proliferation leading to immune dysregulation associated with the pathogenesis of life-threatening infections such as toxic shock syndrome,and necrotizing pneumonia. previously,we demonstrated that staphylococcal enterotoxin-like toxin x (selx) from staphylococcus aureus is a classical superantigen that exhibits t-cell activation in a vβ-specific manner,and contributes to the pathogenesis of necrotizing pneumonia. here,we discovered that selx can also bind to neutrophils from human and other mammalian species and disrupt igg-mediated phagocytosis. site-directed mutagenesis of the conserved sialic acid-binding motif of selx abolished neutrophil binding and phagocytic killing,and revealed multiple glycosylated neutrophil receptors for selx binding. furthermore,the neutrophil binding-deficient mutant of selx retained its capacity for t-cell activation demonstrating that selx exhibits mechanistically independent activities on distinct cell populations associated with acquired and innate immunity,respectively. finally,we demonstrated that the neutrophil-binding activity rather than superantigenicity is responsible for the selx-dependent virulence observed in a necrotizing pneumonia rabbit model of infection. taken together,we report the first example of a sag,that can manipulate both the innate and adaptive arms of the human immune system during s. aureus pathogenesis. © 2017 tuffs et al.