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"A syndrome so characteristic" Molecular and clinical studies of Fusobacterium necrophorum and Lemierre's syndrome

Holm, Karin LU (2015) In Lund University, Faculty of Medicine Doctoral Dissertation Series 2015:128.
Abstract
Lemierre’s syndrome is caused by Fusobacterium necrophorum and involves tonsillitis, jugular vein thrombophlebitis and septic pulmonary emboli. The first studies underlying this thesis focused on bacterial interaction with coagulation. The contact system initiates the intrinsic pathway of coagulation and the release of the pro-inflammatory peptide bradykinin. We found that the contact system was activated at the surface of F. necrophorum, which may contribute the pathogenesis of thrombosis in Lemierre’s syndrome. We also found that plasminogen of the fibrinolytic system may be recruited to and activated at the surface of F. necrophorum, which may be of importance for invasion and dissemination. To examine if host factors affecting... (More)
Lemierre’s syndrome is caused by Fusobacterium necrophorum and involves tonsillitis, jugular vein thrombophlebitis and septic pulmonary emboli. The first studies underlying this thesis focused on bacterial interaction with coagulation. The contact system initiates the intrinsic pathway of coagulation and the release of the pro-inflammatory peptide bradykinin. We found that the contact system was activated at the surface of F. necrophorum, which may contribute the pathogenesis of thrombosis in Lemierre’s syndrome. We also found that plasminogen of the fibrinolytic system may be recruited to and activated at the surface of F. necrophorum, which may be of importance for invasion and dissemination. To examine if host factors affecting coagulation and invasion could be important in Lemierre’s syndrome we conducted a retrospective study of 65 patients with Lemierre’s syndrome or other invasive infection with F. necrophorum. Patients with Lemierre’s syndrome were screened for underlying thrombophilia and concomitant Epstein-Barr virus (EBV) infection and the clinical spectrum was described. On admittance, patients with Lemierre’s syndrome were severely ill, in a majority fulfilling the criteria for severe sepsis. Underlying thrombophilia was not over-represented in patients with Lemierre’s syndrome and concomitant EBV infection was uncommon. Finally, we found that the gene coding for leukotoxin, a well-known virulence factor for the animal subspecies, was present in human isolates and that there were three types of sequences, of which two were novel. Only a minority of the isolates had a leukotoxin gene of the previously described sequence type. This thesis provides new information about potential bacterial virulence factors, host factors and host-pathogen interactions that may be of importance for F. necrophorum infection and adds to the knowledge of the clinical spectrum of invasive infections with F. necrophorum. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Bergman, Peter, Karolinska Institute
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Fusobacterium necrophorum, Lemierre’s syndrome, contact system, fibrinolysis, thrombophilia, leukotoxin
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
volume
2015:128
pages
86 pages
publisher
Infection medicine
defense location
Belfragesalen, BMC D15, Klinikgatan 32, Lund
defense date
2015-12-04 13:00
ISSN
1652-8220
ISBN
978-91-7619-208-5
language
English
LU publication?
yes
id
38f81245-d376-49cd-88f5-79f7a148e54d (old id 8310471)
date added to LUP
2015-12-14 16:06:10
date last changed
2016-09-19 08:44:51
@phdthesis{38f81245-d376-49cd-88f5-79f7a148e54d,
  abstract     = {Lemierre’s syndrome is caused by Fusobacterium necrophorum and involves tonsillitis, jugular vein thrombophlebitis and septic pulmonary emboli. The first studies underlying this thesis focused on bacterial interaction with coagulation. The contact system initiates the intrinsic pathway of coagulation and the release of the pro-inflammatory peptide bradykinin. We found that the contact system was activated at the surface of F. necrophorum, which may contribute the pathogenesis of thrombosis in Lemierre’s syndrome. We also found that plasminogen of the fibrinolytic system may be recruited to and activated at the surface of F. necrophorum, which may be of importance for invasion and dissemination. To examine if host factors affecting coagulation and invasion could be important in Lemierre’s syndrome we conducted a retrospective study of 65 patients with Lemierre’s syndrome or other invasive infection with F. necrophorum. Patients with Lemierre’s syndrome were screened for underlying thrombophilia and concomitant Epstein-Barr virus (EBV) infection and the clinical spectrum was described. On admittance, patients with Lemierre’s syndrome were severely ill, in a majority fulfilling the criteria for severe sepsis. Underlying thrombophilia was not over-represented in patients with Lemierre’s syndrome and concomitant EBV infection was uncommon. Finally, we found that the gene coding for leukotoxin, a well-known virulence factor for the animal subspecies, was present in human isolates and that there were three types of sequences, of which two were novel. Only a minority of the isolates had a leukotoxin gene of the previously described sequence type. This thesis provides new information about potential bacterial virulence factors, host factors and host-pathogen interactions that may be of importance for F. necrophorum infection and adds to the knowledge of the clinical spectrum of invasive infections with F. necrophorum.},
  author       = {Holm, Karin},
  isbn         = {978-91-7619-208-5},
  issn         = {1652-8220},
  keyword      = {Fusobacterium necrophorum,Lemierre’s syndrome,contact system,fibrinolysis,thrombophilia,leukotoxin},
  language     = {eng},
  pages        = {86},
  publisher    = {Infection medicine},
  school       = {Lund University},
  series       = {Lund University, Faculty of Medicine Doctoral Dissertation Series},
  title        = {"A syndrome so characteristic" Molecular and clinical studies of Fusobacterium necrophorum and Lemierre's syndrome},
  volume       = {2015:128},
  year         = {2015},
}