A study on the inhibitory action of vitronnectin on staphylococcal leukocidin and gamma-hemolysin

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Staphylococcal γ-hemolysin and leukocidin are bi-component cytolysins, consisting of LukF (or Hlg1)/Hlg2 and LukF/LukS, respectively. We have previously purified a serum inhibitor of γ-hemolysin and leukocidin, and identified it as vitronectin. In this study, we showed that (i) vitronectin fragments specifically bound to the Hlg2 component of γ-hemolysin and the LukS component of leukocidin to prevent the toxin-induced lysis of human erythrocytes and human polymorphonuclear leukocytes, respectively, (ii) vitronectin fragments and Hlg2 component (or LukS component) formed high-molecular-weight complexes that co-sedimented in a sucrose gradient centrifugation and co-migrated on a native polyacrylamide gel electrophoresis, (iii) the co-sedimented complexes contained vitronectin and the toxin component in an approximate molar ratio of 6 : 1, and (iv) the complexes had spherical shape with diameter of approximately 20 nm. The ability of γ-hemolysin and leukocidin to bind vitronectin is a novel function of the pore-forming cytolysins.