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* Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Finland;
Department of Otorhinolaryngology, Helsinki University Central Hospital, Helsinki, Finland; and
HUSLAB, Helsinki University Central Hospital, Finland
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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This study was supported by the Sigrid Juselius Foundation, the Academy of Finland, and the Helsinki University Central Hospital funds.
2 Address correspondence and reprint requests to Dr. Hanna Jarva, Haartman Institute, Department of Bacteriology and Immunology, P.O. Box 21, Fin-00014 University of Helsinki, Helsinki, Finland. E-mail address: hanna.jarva{at}helsinki.fi
3 Abbreviations used in this paper: MAC, membrane attack complex; fH, factor H; AP, alternative pathway; C4BP, C4b-binding protein; FAA, fastidious anaerobic agar; VBS, Veronal-buffered saline; NHS, normal human serum; FHR-1/-4, factor H-related protein-1/-4; HIS, heat-inactivated serum; SCR, short consensus repeat; GVB, gelatin Veronal buffer; FHL-1, factor H-like protein-1; MFI, mean fluorescence intensity.
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  J. Shaughnessy, L. A. Lewis, H. Jarva, and S. Ram Functional Comparison of the Binding of Factor H Short Consensus Repeat 6 (SCR 6) to Factor H Binding Protein from Neisseria meningitidis and the Binding of Factor H SCR 18 to 20 to Neisseria gonorrhoeae Porin Infect. Immun., May 1, 2009; 77(5): 2094 - 2103. [Abstract] [Full Text] [PDF]
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