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.

Human Complement Factor H Binds to Outer Membrane Protein Rck of Salmonella

“…The binding of fH SCRs 5-7 and 19 to 20 to Rck are analogous to those observed with Fusobacterium necrophorum (29) and Borrelia burgdorferi CspA (BbCRASP-1) (30), where the same regions of fH were responsible for binding to the pathogen surface. Binding of fH via a single or multiple SCRs from regions 5-7 or 19 to 20 has been observed in a diverse range of bacterial pathogens, such as S. pyogenes, B. afzelii, B. burgdorferi (30), P. aeruginosa (26), H. influenzae (25), N. gonorrheae (31), N. meningitidis (32) and Y. enterocolitica (28).…”

Factor H-related Protein 4 Activates Complement by Serving as a Platform for the Assembly of Alternative Pathway C3 Convertase via Its Interaction with C3b Protein

“…pathogens, such as Fusobacterium necrophorum (28) and the yeast Candida albicans (29). In our experiments both CFHR4A and FH bound weakly to S. cerevisiae cells (supplemental Fig.…”

Activation of the Contact System at the Surface of Fusobacterium necrophorum Represents a Possible Virulence Mechanism in Lemièrre's Syndrome

“…funduliforme isolates (34), but leukotoxin may not be present in all human invasive isolates (18). Friberg and coworkers showed that binding of factor H is important for complement evasion by the bacterium (8). However, the pathogenesis of the distinctive symptoms of Lemièrre's syndrome is unknown.…”