Heparin-inhibitable lectin activity of the filamentous hemagglutinin adhesin of Bordetella pertussis

Abstract

Bordetella pertussis, the etiologic agent of whooping cough, produces an outer membrane-associated filamentous hemagglutinin (FHA) which is the major adhesin of this organism. FHA exhibits a lectin-like activity for heparin and dextran sulfate. By using in vitro adherence assays to cultured epithelial cells, the attachment of B. pertussis was reduced in the presence of sulfated polysaccharides such as heparin and dextran sulfate but not in the presence of dextran, indicating the crucial role of polysaccharide sulfation. In addition, inhibition of cellular sulfation by chlorate treatment of the cells resulted in a reduction of B. pertussis adherence, suggesting that epithelial cell surface-exposed sulfated glycoconjugates may serve as receptors for the microorganism. B. pertussis mutant strains deficient in FHA production expressed residual adherence that was no longer inhibited by sulfated polysaccharides. In addition, purified FHA displayed heparin-inhibitable binding to epithelial cells. Mapping experiments of the heparin-binding site of FHA indicated that this site is different from the RGD site and the recently proposed carbohydrate-binding site involved in the interaction of FHA with lactosylceramide. This result demonstrates that FHA contains at least three different binding sites, a feature unusual for bacterial adhesins but similar to features of eukaryotic adhesins and extracellular matrix proteins.

Attenuated Bordetella pertussis vaccine strain BPZE1 modulates allergen‐induced immunity and prevents allergic pulmonary pathology in a murine model

“…Mice were exposed to live virulent or attenuated bacteria, and sensitized to allergen during infection. Virulent B. pertussis BPSM [20] and attenuated BPZE1 were cultured as previously described [21]. Attenuated or virulent strains at mid-log growth were administered to mice by aerosol using the respiratory challenge model and standard protocols [16].…”

Pseudomonas aeruginosa uses a cyclic‐di‐GMP‐regulated adhesin to reinforce the biofilm extracellular matrix

“…The presence of an N-terminal carbohydrate binding domain, and the co-regulation of cdrAB with the pel and psl gene clusters led us to propose that CdrA may bind to one of these polysaccharides. There is precedence for sugar binding in this particular family of adhesins (Menozzi et al, 1994b). Like CdrA, expression of FHA of B. pertussis induces liquid culture auto-aggregation.…”

Topology and maturation of filamentous haemagglutinin suggest a new model for two‐partner secretion

“…Previous models for TPS show the TpsA N-terminus emerging first from the outer membrane channel (Henderson et al, 2004;Jacob-Dubuisson et al, 2004;Thanassi et al, 2005) and the N-terminus of FHA has been shown to be involved in carbohydrate-dependent haemagglutination in vitro, suggesting a role in adherence (Sandros and Tuomanen, 1993). A heparin binding domain located near the FHA N-terminus has also been implicated in epithelial cell binding (Menozzi et al, 1994). Although most anti-FHA antibodies generated in response to infection by B. pertussis are directed against the C-terminus (Leininger et al, 1997), this region of the protein was not previously thought to represent a functional domain.…”