C. canimorsus interferes with coagulation by proteolytic cleavage of human coagulation factor X

  • Katrin Hack

Student thesis: Doc typesDoctor of Sciences

Abstract

This work is dedicated to exploring pathogenesis mechanisms of Capnocytophaga canimorsus, a Gram-negative bacterium, which is part of the canine oral microbiota and which predominantly causes dog bite related blood stream infections in humans. In this study we focused on the interaction of C. canimorsus with hemostasis and the inflammatory response triggered by the pathogen.

C. canimorsus infection is often associated with bleeding disorders, such as disseminated intravascular coagulation (DIC). We demonstrate that C. canimorsus expresses a type 7 dipeptidyl peptidase of the S46 serine protease family (CcDPP7), which cleaves the light and heavy chain of human coagulation factor X thereby mediating inhibition of hemostasis. CcDPP7 is active in vivo and we think it could contribute to aggravation of DIC induced hemorrhage. Moreover, since hemostasis is involved in the immune defense, we hypothesize that inhibition of coagulation could represent a mechanism of immune evasion for C. canimorsus.

C. canimorsus feeds on serum and cell surface glycoproteins. Since glycans play a role in receptor recognition and immune signaling, we aimed at clarifying if this property would affect the pro-inflammatory response to the bacteria. We could not prove a strong effect of deglycosylation on secretion of pro-inflammatory cytokines. However, we show that the pro-inflammatory response to C. canimorsus is more elevated than previously reported and that despite earlier findings TLR4 is required for sensing of the pathogen in addition to TLR2.
Date of Award12 Aug 2016
Original languageEnglish
Awarding Institution
  • University of Namur
SupervisorGuy Cornelis (Supervisor), JEAN-JACQUES LETESSON (President), Jean-Michel DOGNE (Jury), Tomas Michiels (Jury), Pierre Bogaerts (Jury) & Bernard Chatelain (Jury)

Attachment to an Research Institute in UNAMUR

  • NARILIS

Keywords

  • hemostasis
  • infection
  • factor X
  • C. canimorsus
  • coagulation
  • innate immunity
  • protease
  • DPP7
  • glycobiology

Cite this

C. canimorsus interferes with coagulation by proteolytic cleavage of human coagulation factor X
Hack, K. (Author). 12 Aug 2016

Student thesis: Doc typesDoctor of Sciences