Activation of the Contact System at the Surface of Fusobacterium necrophorum Represents a Possible Virulence Mechanism in Lemièrre's Syndrome
Open Access
- 1 August 2011
- journal article
- research article
- Published by American Society for Microbiology in Infection and Immunity
- Vol. 79 (8), 3284-3290
- https://doi.org/10.1128/iai.05264-11
Abstract
Fusobacterium necrophorum causes Lemièrre's syndrome, a serious disease with septic thrombophlebitis of the internal jugular vein, pulmonary involvement, and systemic inflammation. The contact system is a link between inflammation and coagulation, and contact activation by the bacteria could therefore contribute to the abnormal coagulation and inflammation seen in patients with Lemièrre's syndrome. In this study, F. necrophorum was found to bind radiolabeled high-molecular-weight kininogen (HK), a central component of the contact system. Binding was inhibited by the addition of unlabeled HK and domain D5 of HK but not other components of the contact system, indicating a specific interaction mediated through the D5 region. Binding of HK was significantly reduced after pretreatment of the bacteria with trypsin, suggesting that surface proteins are involved in HK binding. Incubation of the bacteria with human plasma resulted in an HK breakdown pattern suggestive of bradykinin release, and bradykinin was also detected in the supernatant. In addition, we show that factor XI (FXI), another component of the contact system, binds to F. necrophorum and that the bound FXI reconstitutes the activated partial thromboplastin time of FXI-deficient plasma. Thrombin activity was detected at the surface of the bacteria following incubation with plasma, indicating that the intrinsic pathway of coagulation is activated at the surface. This activity was completely blocked by inhibitors of the contact system. The combined results show that the contact system is activated at the surface of F. necrophorum , suggesting a pathogenic role for this system in Lemièrre's syndrome.This publication has 40 references indexed in Scilit:
- Adsorption of Components of the Plasma Kinin-Forming System on the Surface ofPorphyromonas gingivalisInvolves Gingipains as the Major Docking PlatformsInfection and Immunity, 2011
- A role for factor XIIa–mediated factor XI activation in thrombus formation in vivoBlood, 2010
- Binding and activation of the human plasma kinin-forming system on the cell walls of Candida albicans and Candida tropicalisBiological Chemistry, 2010
- Platelet Polyphosphates Are Proinflammatory and Procoagulant Mediators In VivoCell, 2009
- Assembly, activation, and physiologic influence of the plasma kallikrein/kinin systemInternational Immunopharmacology, 2008
- Identification of lipopolysaccharide binding site on high molecular weight kininogenBiochemical and Biophysical Research Communications, 2008
- Human Infection withFusobacterium necrophorum(Necrobacillosis), with a Focus on Lemierre's SyndromeClinical Microbiology Reviews, 2007
- Detection of Fusobacterium necrophorum subsp. funduliforme in tonsillitis in young adults by real-time PCRClinical Microbiology & Infection, 2007
- The contact system—a novel branch of innate immunity generating antibacterial peptidesThe EMBO Journal, 2006
- The Relative Priority of Prekallikrein and Factors XI/XIa Assembly on Cultured Endothelial CellsPublished by Elsevier BV ,2003