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Infection and Immunity, March 2008, p. 1093-1104, Vol. 76, No. 3
0019-9567/08/$08.00+0     doi:10.1128/IAI.01349-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Novel Adhesin from Pasteurella multocida That Binds to the Integrin-Binding Fibronectin FnIII_9-10 Repeats

Division of Microbial Diseases, UCL Eastman Dental Institute, University College London, 256 Gray's Inn Road, London WC1X 8LD, United Kingdom,¹ Department of Biochemistry and Molecular Biology, University College London, Gower Street, London WC1E 6BT, United Kingdom,² Department of Pathology and Infectious Diseases, Royal Veterinary College, Hawkshead Lane, North Mimms, Herts AL9 7TA, United Kingdom,³ School of Crystallography, Birkbeck College, University of London, Malet St., London WC1E 7HX, United Kingdom⁴

Received 8 October 2007/ Returned for modification 22 November 2007/ Accepted 16 December 2007

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.

Published ahead of print on 26 December 2007.

Editor: A. Camilli