Haemophilus influenzae surface fibrils contribute to serum resistance by interacting with vitronectin.
Vitronectin inhibits the membrane attack complex of the complement system and is found both in plasma and the extracellular matrix. In this study, we have identified the outer membrane protein Haemophilus surface fibrils (Hsf) as the major vitronectin-binding protein in encapsulated H. influenzae type b. A H. influenzae mutant devoid of Hsf showed a significantly decreased binding to both soluble and immobilized vitronectin as compared with the wild-type counterpart. Moreover, Escherichia coli-expressing Hsf at the surface strongly adhered to immobilized vitronectin. Importantly, the H. influenzae Hsf mutant had a markedly reduced survival as compared with the wild-type bacterium when incubated with normal human serum. A series of truncated Hsf fragments were recombinantly manufactured in E. coli. The vitronectin binding regions were located within two separate binding domains. In conclusion, Hsf interacts with vitronectin and thereby inhibits the complement-mediated bactericidal activity, and thus is a major H. influenzae virulence factor.
Hallström
Teresia
T
Medical Microbiology, Department of Laboratory Medicine, Lund University, Malmö University Hospital, Malmö, Sweden.
Trajkovska
Elena
E
Forsgren
Arne
A
Riesbeck
Kristian
K
D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000595:Amino Acid Sequence; D001667:Binding, Competitive / Q000276:immunology; D001770:Blood Bactericidal Activity / Q000235:genetics / Q000276:immunology*; D015938:Complement Membrane Attack Complex / Q000037:antagonists & inhibitors / Q000502:physiology; D004306:Dose-Response Relationship, Immunologic; D019741:Haemophilus influenzae type b / Q000235:genetics / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity; D006493:Heparin / Q000378:metabolism / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D011485:Protein Binding / Q000276:immunology; D017434:Protein Structure, Tertiary; D044967:Serum / Q000276:immunology / Q000382:microbiology; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D019096:Vitronectin / Q000037:antagonists & inhibitors / Q000378:metabolism*
D018829:Adhesins, Bacterial; D015938:Complement Membrane Attack Complex; C102673:Hsf protein, bacteria; D010446:Peptide Fragments; D037521:Virulence Factors; D019096:Vitronectin; D006493:Heparin