title: Factor H binding as a complement evasion mechanism for an anaerobic pathogen, Fusobacterium necrophorum.
abstract: Fusobacterium necrophorum subspecies funduliforme is an obligate anaerobic Gram-negative rod causing invasive infections such as the life-threatening Lemierre's syndrome (sore throat, septicemia, jugular vein thrombosis, and disseminated infection). The aim of our study was to understand if and how F. necrophorum avoids C activation. We studied 12 F. necrophorum subsp. funduliforme strains isolated from patients with sepsis. All strains were resistant to serum killing after a 1-h incubation in 20% serum. The bacteria bound, at different levels, the C inhibitor factor H (fH). Binding was ionic and specific in nature and occurred via sites on both the N terminus and the C terminus of fH. Bound fH remained functionally active as a cofactor for factor I in the cleavage of C3b. Interestingly, patients with the most severe symptoms carried strains with the strongest ability to bind fH. An increased C3b deposition and membrane attack complex formation on the surface of a weakly fH-binding strain was observed and its survival in serum at 3.5 h was impaired. This strain had not caused a typical Lemierre's syndrome. These data, and the fact that fH-binding correlated with the severity of disease, suggest that the binding of fH contributes to virulence and survival of F. necrophorum subsp. funduliforme in the human host. Our data show, for the first time, that an anaerobic bacterium is able to bind the C inhibitor fH to evade C attack.
authors.affiliation: Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Helsinki, Finland
authors.forename: Nathalie
authors.initials: N
authors.lastname: Friberg
authors.forename: Petteri
authors.initials: P
authors.lastname: Carlson
authors.forename: Erna
authors.initials: E
authors.lastname: Kentala
authors.forename: Petri S
authors.initials: PS
authors.lastname: Mattila
authors.forename: Pentti
authors.initials: P
authors.lastname: Kuusela
authors.forename: Seppo
authors.initials: S
authors.lastname: Meri
authors.forename: Hanna
authors.initials: H
authors.lastname: Jarva
mesh_terms: D000693:Anaerobiosis / Q000276:immunology; D001422:Bacterial Adhesion / Q000276:immunology*; D001770:Blood Bactericidal Activity / Q000276:immunology*; D003179:Complement C3b / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology; D017242:Complement Factor H / Q000378:metabolism / Q000502:physiology; D003170:Complement Pathway, Alternative / Q000276:immunology*; D017077:Culture Media, Conditioned; D004306:Dose-Response Relationship, Immunologic; D005675:Fusobacterium necrophorum / Q000254:growth & development* / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D011485:Protein Binding / Q000276:immunology; D013211:Staphylococcus aureus / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity; D013296:Streptococcus pneumoniae / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity
chemical_list: C493495:CFH protein, human; D017077:Culture Media, Conditioned; D003179:Complement C3b; D017242:Complement Factor H