title: Activation of the contact-phase system on bacterial surfaces--a clue to serious complications in infectious diseases.
abstract: Fever, hypotension and bleeding disorders are common symptoms of sepsis and septic shock. The activation of the contact-phase system is thought to contribute to the development of these severe disease states by triggering proinflammatory and procoagulatory cascades; however, the underlying molecular mechanisms are obscure. Here we report that the components of the contact-phase system are assembled on the surface of Escherichia coli and Salmonella through their specific interactions with fibrous bacterial surface proteins, curli and fimbriae. As a consequence, the proinflammatory pathway is activated through the release of bradykinin, a potent inducer of fever, pain and hypotension. Absorption of contact-phase proteins and fibrinogen by bacterial surface proteins depletes relevant coagulation factors and causes a hypocoagulatory state. Thus, the complex interplay of microbe surface proteins and host contact-phase factors may contribute to the symptoms of sepsis and septic shock.
authors.affiliation: Department of Cell and Molecular Biology, Lund University, Sweden. Heiko.Herwald@medkem.lu.se
authors.forename: H
authors.initials: H
authors.lastname: Herwald
authors.forename: M
authors.initials: M
authors.lastname: Mörgelin
authors.forename: A
authors.initials: A
authors.lastname: Olsén
authors.forename: M
authors.initials: M
authors.lastname: Rhen
authors.forename: B
authors.initials: B
authors.lastname: Dahlbäck
authors.forename: W
authors.initials: W
authors.lastname: Müller-Esterl
authors.forename: L
authors.initials: L
authors.lastname: Björck
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D001778:Blood Coagulation Disorders / Q000209:etiology; D001920:Bradykinin / Q000378:metabolism*; D004756:Enterobacteriaceae Infections / Q000503:physiopathology*; D004927:Escherichia coli Infections / Q000503:physiopathology; D005260:Female; D005334:Fever / Q000209:etiology; D007022:Hypotension / Q000209:etiology; D007249:Inflammation / Q000209:etiology; D051379:Mice; D012481:Salmonella Infections, Animal / Q000503:physiopathology; D012772:Shock, Septic / Q000209:etiology*
chemical_list: D001426:Bacterial Proteins; D001920:Bradykinin