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

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.