6533b823fe1ef96bd127ec62

RESEARCH PRODUCT

Activation of the contact-phase system on bacterial surfaces--a clue to serious complications in infectious diseases.

Lars BjörckBjörn DahlbäckMatthias MörgelinArne OlsénWerner Müller-esterlHeiko HerwaldMikael Rhen

subject

FeverFimbriaBradykininBiologyFibrinogenBradykininGeneral Biochemistry Genetics and Molecular BiologyProinflammatory cytokineMicrobiologySepsischemistry.chemical_compoundMiceBacterial ProteinsmedicineAnimalsEscherichia coli InfectionsInflammationSalmonella Infections AnimalSeptic shockEnterobacteriaceae InfectionsGeneral MedicineBlood Coagulation Disordersmedicine.diseaseShock SepticCoagulationchemistryShock (circulatory)ImmunologyFemalemedicine.symptomHypotensionmedicine.drug

description

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.

10.1038/nm0398-298https://pubmed.ncbi.nlm.nih.gov/9500598