title: A fine-tuned interaction between trimeric autotransporter haemophilus surface fibrils and vitronectin leads to serum resistance and adherence to respiratory epithelial cells.
abstract: Haemophilus influenzae type b (Hib) escapes the host immune system by recruitment of the complement regulator vitronectin, which inhibits the formation of the membrane attack complex (MAC) by inhibiting C5b-C7 complex formation and C9 polymerization. We reported previously that Hib acquires vitronectin at the surface by using Haemophilus surface fibrils (Hsf). Here we studied in detail the interaction between Hsf and vitronectin and its role in the inhibition of MAC formation and the invasion of lung epithelial cells. The vitronectin-binding region of Hsf was defined at the N-terminal region comprising Hsf amino acids 429 to 652. Moreover, the Hsf recognition site on vitronectin consisted of the C-terminal amino acids 352 to 374. H. influenzae was killed more rapidly in vitronectin-depleted serum than in normal human serum (NHS), and increased MAC deposition was observed at the surface of an Hsf-deficient H. influenzae mutant. In parallel, Hsf-expressing Escherichia coli selectively acquired vitronectin from serum, resulting in significant inhibition of the MAC. Moreover, when vitronectin was bound to Hsf, increased bacterial adherence and internalization into epithelial cells were observed. Taking our findings together, we have defined a fine-tuned protein-protein interaction between Hsf and vitronectin that may contribute to increased Hib virulence.
authors.affiliation: Medical Microbiology, Department of Laboratory Medicine Malmö, Lund University, Malmö, Sweden.
authors.forename: Birendra
authors.initials: B
authors.lastname: Singh
authors.forename: Yu-Ching
authors.initials: YC
authors.lastname: Su
authors.forename: Tamim
authors.initials: T
authors.lastname: Al-Jubair
authors.forename: Oindrilla
authors.initials: O
authors.lastname: Mukherjee
authors.forename: Teresia
authors.initials: T
authors.lastname: Hallström
authors.forename: Matthias
authors.initials: M
authors.lastname: Mörgelin
authors.forename: Anna M
authors.initials: AM
authors.lastname: Blom
authors.forename: Kristian
authors.initials: K
authors.lastname: Riesbeck
mesh_terms: D018829:Adhesins, Bacterial / Q000502:physiology*; D000704:Analysis of Variance; D001667:Binding, Competitive; D001770:Blood Bactericidal Activity / Q000276:immunology*; D002448:Cell Adhesion / Q000502:physiology*; D015938:Complement Membrane Attack Complex / Q000502:physiology; D004306:Dose-Response Relationship, Immunologic; D019741:Haemophilus influenzae type b / Q000276:immunology* / Q000472:pathogenicity; D006493:Heparin / Q000502:physiology; D006801:Humans; D044967:Serum / Q000276:immunology / Q000382:microbiology; D019096:Vitronectin / Q000378:metabolism*
chemical_list: D018829:Adhesins, Bacterial; D015938:Complement Membrane Attack Complex; C102673:Hsf protein, bacteria; D019096:Vitronectin; D006493:Heparin