Vitronectin and its fragments purified as serum inhibitors of Staphylococcus aureus gamma-hemolysin and leukocidin, and their specific binding to the hlg2 and the LukS components of the toxins.
Staphylococcal gamma-hemolysin and leukocidin are bi-component cytolysins, consisting of LukF (or Hlg1)/Hlg2 and LukF/LukS, respectively. Here, we purified serum inhibitors of gamma-hemolysin and leukocidin from human plasma. Protein sequencing showed that the purified inhibitors of 62, 57, 50 and 38 kDa were the vitronectin fragments with truncation(s) of the C-terminal or both N- and C-terminal regions. The purified vitronectin fragments specifically bound to the Hlg2 component of gamma-hemolysin and the LukS component of leukocidin to form high-molecular-weight complexes with them, leading to inhibition of the toxin-induced lysis of human erythrocytes and human polymorphonuclear leukocytes, respectively. Intact vitronectin also showed inhibitory activity to the toxins. The ability of gamma-hemolysin and leukocidin to bind vitronectin and its fragments is a novel function of the pore-forming cytolysins.
Katsumi
H
H
Department of Molecular and Cellular Biology, Graduate School of Agricultural Science, Tohoku University, Aoba-ku, Sendai, Japan.
Tomita
T
T
Kaneko
J
J
Kamio
Y
Y
D000595:Amino Acid Sequence; D000992:Antitoxins / Q000097:blood / Q000302:isolation & purification / Q000502:physiology*; D001426:Bacterial Proteins; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors* / Q000097:blood; D015153:Blotting, Western; D005591:Chemical Fractionation; D006460:Hemolysin Proteins / Q000097:blood; D006801:Humans; D015151:Immunoblotting; D007956:Leukocidins / Q000037:antagonists & inhibitors* / Q000097:blood / Q000302:isolation & purification; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000097:blood / Q000302:isolation & purification / Q000502:physiology*; D011485:Protein Binding; D019096:Vitronectin / Q000097:blood / Q000302:isolation & purification / Q000502:physiology*
D000992:Antitoxins; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D006460:Hemolysin Proteins; D007956:Leukocidins; D010446:Peptide Fragments; D019096:Vitronectin; C037956:gamma-hemolysin, Staphylococcus aureus; C108483:leukocidin S-component protein, Staphylococcus