Activation of the contact-phase system on bacterial surfaces--a clue to serious complications in infectious diseases.
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.
Herwald
H
H
Department of Cell and Molecular Biology, Lund University, Sweden. Heiko.Herwald@medkem.lu.se
Mörgelin
M
M
Olsén
A
A
Rhen
M
M
Dahlbäck
B
B
Müller-Esterl
W
W
Björck
L
L
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*
D001426:Bacterial Proteins; D001920:Bradykinin