Impaired plasma clottability induction through fibrinogen degradation by ASP, a serine protease released from Aeromonas sobria.
Aeromonas sobria infection often advances to sepsis, in which interaction of bacterial components with plasma proteins possibly causes various disorders. This bacterium releases a serine protease (ASP), a putative virulence factor, and binds to fibrinogen. To study the ASP effect on fibrinogen, we incubated fibrinogen or plasma with ASP and investigated their clotting elicited by thrombin, which converts fibrinogen to a fibrin clot. Enzymatically active ASP retarded plasma clotting in a dose-dependent manner starting at an ASP concentration of 10 nM. ASP also retarded fibrinogen clotting at 3 nM and above, which appeared to correspond to ASP cleavage of fibrinogen at the A alpha-chain. Consistent with containing serine protease activity for an ASP-specific substrate, the culture supernatant of an ASP gene-introduced strain retarded plasma and fibrinogen clotting more than that of the wild-type strain. The culture supernatant of an ASP gene-disrupted strain that releases negligible serine protease activity for the ASP-specific substrate did not affect plasma clotting. These results indicate that ASP is the main fibrinogenolytic protease released from A. sobria. Impaired plasma clottability induction through fibrinogen degradation is a new virulence activity of ASP and may contribute to hemorrhagic tendencies in sepsis caused by infection with this bacterium.
Imamura
Takahisa
T
Department of Molecular Pathology, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan. taka@gpo.kumamoto-u.ac.jp
Nitta
Hidetoshi
H
Wada
Yoshihiro
Y
Kobayashi
Hidetomo
H
Okamoto
Keinosuke
K
D000333:Aeromonas / Q000201:enzymology* / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D001777:Blood Coagulation / Q000187:drug effects*; D005340:Fibrinogen / Q000378:metabolism*; D017353:Gene Deletion; D012697:Serine Endopeptidases / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D013917:Thrombin / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism
D001426:Bacterial Proteins; D014764:Viral Proteins; C407905:virulence factor p28, Ectromelia virus; D005340:Fibrinogen; D012697:Serine Endopeptidases; D013917:Thrombin