Comparative roles of the Arg-Gly-Asp sequence present in the Bordetella pertussis adhesins pertactin and filamentous hemagglutinin

Abstract

Pertactin and filamentous hemagglutinin (FHA), proteins present on the surface of the gram-negative organism Bordetella pertussis, have been shown to contain the putative cell-binding sequence arginine-glycineaspartic acid (RGD) and to promote eukaryotic cell attachment. The attachment of epithelial cells to purified pertactin and the entry of B. pertussis into human HeLa cells are both inhibited by an RGD-containing peptide derived from the pertactin sequence. In contrast, an RGD-containing peptide derived from the FHA sequence has no effect on either the attachment of epithelial cells to purified FHA or the entry of B. pertussis into HeLa cells. Staphylococcus aureus organisms coated with pertactin or FHA, purified from B. pertussis, enter HeLa cells more efficiently than S. aureus cells coated with bovine serum albumin. The pertactin-enhanced entry of S. aureus is inhibited by 75% in the presence of the RGD peptide from pertactin, whereas the RGD peptide derived from FHA has no effect on the increased entry promoted by the pertactin-coated or by the FHA-coated S. aureus. These results indicate that the active uptake of B. pertussis by certain mammalian cells may be mediated by the interaction of the RGD site found in pertactin with eukaryotic cell surface receptors.

Pertussis: a matter of immune modulation

“…In contrast, the same mutant was found to be significantly attenuated for invasion in a human laryngeal epithelial cell model (Bassinet et al, 2000). A role for Prn in invasion was further supported by the observation that this process was inhibited in the presence of peptides derived from Prn with the RGD motif (Leininger et al, 1992). Based on the last two studies, it seems plausible that Prn contributes to the ability of B. pertussis to bind and invade respiratory epithelial cells, but the underlying molecular mechanism has not yet been resolved.…”

The filamentous haemagglutinin, a multifaceted adhesin produced by virulent Bordetella spp.

“…Interestingly, the motif containing the asparagines can also be found in other outer surface proteins possibly involved in bacterial attachment ( Fig. 3), such as the HMW1 and HMW2 of Haemophilus influenzae (Barenkamp and Leininger, 1992). This observation suggests that these proteins are exported by a similar mechanism and that, consequently, H. influenzae also contains a gene homologous to fhaC.…”

Tracheal colonization factor: a Bordetella pertussis secreted virulence determinant

“…Recent data indicate that the RGD of FHA may be involved in recognition ofthe monocyte leukocyte response integrin-integrin associated protein complex and stimulation of GR3 binding of FHA (Ishibashi etal., 1994). The pertactin RGD has been shown to be involved in adherence to epithelial cell lines (Leininger et al, 1992). The function of BrkA and Tcf RGD is unknown.…”