Induction of vascular leakage through release of bradykinin and a novel kinin by cysteine proteinases from Staphylococcus aureus.
Staphylococcus aureus is a major pathogen of gram-positive septic shock and frequently is associated with consumption of plasma kininogen. We examined the vascular leakage (VL) activity of two cysteine proteinases that are secreted by S. aureus. Proteolytically active staphopain A (ScpA) induced VL in a bradykinin (BK) B(2)-receptor-dependent manner in guinea pig skin. This effect was augmented by staphopain B (SspB), which, by itself, had no VL activity. ScpA also produced VL activity from human plasma, apparently by acting directly on kininogens to release BK, which again was augmented significantly by SspB. Intravenous injection of ScpA into a guinea pig caused BK B(2)-receptor-dependent hypotension. ScpA and SspB together induced the release of leucyl-methionyl-lysyl-BK, a novel kinin with VL and blood pressure-lowering activities that are equivalent to BK. Collectively, these data suggest that production of BK and leucyl-methionyl-lysyl-BK by staphopains is a new mechanism of S. aureus virulence and bacterial shock. Therefore, staphopain-specific inhibitors and kinin-receptor antagonists could be used to treat this disease.
Imamura
Takahisa
T
Division of Molecular Pathology, Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto 860-8556, Japan. taka@kaiju.medic.kumamoto-u.ac.jp
Tanase
Sumio
S
Szmyd
Grzegorz
G
Kozik
Andrzej
A
Travis
James
J
Potempa
Jan
J
D000818:Animals; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000378:metabolism / Q000473:pathology*; D001920:Bradykinin / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000008:administration & dosage / Q000378:metabolism*; D005260:Female; D006168:Guinea Pigs; D007022:Hypotension / Q000139:chemically induced; D007275:Injections, Intravenous; D008297:Male; D043782:Receptor, Bradykinin B2; D013203:Staphylococcal Infections / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D013211:Staphylococcus aureus / Q000201:enzymology* / Q000472:pathogenicity
D001426:Bacterial Proteins; D043782:Receptor, Bradykinin B2; D003546:Cysteine Endopeptidases; C501295:staphopain A protein, Staphylococcus aureus; C479137:staphopain B protein, Staphylococcus aureus; D001920:Bradykinin