Serum resistance in an invasive, nontypeable Haemophilus influenzae strain.
A common feature of many different organisms causing bacteremia is the ability to avoid the bactericidal effects of normal human serum. In Haemophilus influenzae encapsulated strains are particularly serum resistant; however, we found that a nonencapsulated strain (R2866) isolated from the blood of an immunocompetent child with meningitis who had been successfully immunized with H. influenzae type b conjugate vaccine was serum resistant. Since serum resistance usually involves circumventing the action of the complement system, we defined the deposition of various complement components on the surfaces of this H. influenzae strain (R2866), a nonencapsulated avirulent laboratory strain (Rd), and a virulent type b encapsulated strain (Eagan). Membrane attack complex (MAC) accumulation correlated with the loss of bacterial viability; correspondingly, the rates of MAC deposition on the serum-sensitive strain Rd and the serum-resistant strains differed. Analysis of cell-associated immunoglobulin G (IgG), C1q, C3b, and C5b indicated that serum-resistant H. influenzae prevents MAC accumulation by delaying the synthesis of C3b through the classical pathway. Among the initiators of the classical pathway, IgG deposition contributes most of the C3 convertase activity necessary to start the cascade ending with MAC deposition. Despite similar IgG binding, strain R2866 delays C3 convertase activity compared to strain Rd. We conclude that strain R2866 can persist in the bloodstream, in part by inhibiting or delaying C3 deposition on the cell surface, escaping complement mediated killing.
Williams
B J
BJ
Department of Molecular Microbiology and Immunology, University of Missouri-Columbia, Columbia, Missouri 65212, USA.
Morlin
G
G
Valentine
N
N
Smith
A L
AL
D016667:Bacterial Capsules / Q000502:physiology; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology; D001770:Blood Bactericidal Activity; D003176:Complement C3 / Q000502:physiology; D017242:Complement Factor H / Q000502:physiology; D015938:Complement Membrane Attack Complex / Q000502:physiology; D003171:Complement Pathway, Classical; D006193:Haemophilus influenzae / Q000276:immunology*; D006801:Humans; D008070:Lipopolysaccharides / Q000032:analysis; D010767:Phosphorylcholine / Q000032:analysis
D001425:Bacterial Outer Membrane Proteins; C493495:CFH protein, human; D003176:Complement C3; D015938:Complement Membrane Attack Complex; D008070:Lipopolysaccharides; C023023:lipid-linked oligosaccharides; D010767:Phosphorylcholine; D017242:Complement Factor H