Novel adhesin from Pasteurella multocida that binds to the integrin-binding fibronectin FnIII9-10 repeats

Mullen, Lisa M, Nair, Sean P, Ward, John M, Rycroft, Andrew N, Williams, Rachel J, Robertson, Giles, Mordan, Nicky J and Henderson, Brian (2008) Novel adhesin from Pasteurella multocida that binds to the integrin-binding fibronectin FnIII9-10 repeats. Infection and Immunity, 76 (3). pp. 1093-1104. ISSN 0019-9567

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Phage display screening with fragmented genomic DNA from the animal pathogen Pasteurella multocida has identified a gene encoding a putative fibronectin binding protein (19). Homologues of this gene (PM1665) are found in all other sequenced members of the Pasteurellaceae. Gene PM1665 has been cloned, and the protein has been expressed. Recombinant PM1665 protein binds to both soluble and immobilized fibronectin and is unique in that it interacts with the integrin-binding fibronectin type III (FnIII) repeats FnIII(9-10) and not, as is the case for almost all other fibronectin adhesins, to the N-terminal type I repeats. Surface plasmon resonance analysis revealed a complex binding mechanism with a K(D) (equilibrium dissociation constant) of 150 nM +/- 70 nM. Bioinformatics analysis suggests that the PM1665 protein contains two helix-hairpin-helix (HhH) motifs, and truncation mutation studies have identified the binding site in the protein as a combination of these two HhH motifs in conjunction with a conserved amino acid motif, VNINTA. We have shown that the PM1665 protein is on the cell surface and that binding of P. multocida to fibronectin is almost completely inhibited by anti-PM1665 antiserum. These results support the hypothesis that the PM1665 protein is a member of a new family of fibronectin binding adhesins that are important in the adhesion of P. multocida to fibronectin.

Item Type: Article
Schools and Departments: Brighton and Sussex Medical School > Clinical and Experimental Medicine
Subjects: Q Science > QR Microbiology > QR0171 Microorganisms in the animal body
Depositing User: Lisa Mullen
Date Deposited: 18 Jan 2013 10:45
Last Modified: 05 Oct 2017 18:27
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