Characterization of the Binding Region for the Yersinia Enterocolitica Adhesin YadA on Types I and II Collagen
Overview
Affiliations
Objective: The plasmid-encoded adhesin YadA confers pathogenic functions on Yersinia enterocolitica, a microorganism associated with reactive arthritis. While emerging evidence has indicated that the persistence of the bacteria in individuals with reactive arthritis is a prerequisite for the development of the disease, the tissue specificity of this immunologic disease sequela remains elusive. The present study was undertaken to investigate YadA-mediated binding of Y enterocolitica to the most abundant collagens in joints, types I and II collagen.
Methods: Binding studies were performed with recombinant Y enterocolitica strains and highly purified type II collagen and the alpha 1(I) chain of type I collagen, or fragments of these collagens generated by various enzymatic and nonenzymatic cleavage procedures. Interactions of bacteria with the proteins were determined in binding assays with radiolabeled proteins.
Results: Binding regions for YadA were identified at the 181-amino acid fragment alpha 1(I)78CBN of type I collagen and the CB10 fragment of type II collagen. From binding and blocking experiments with alpha 1(I) fragments, cyanogen bromide-derived or mammalian collagenase-derived type II collagen fragments, and synthetic peptides with collagen-like structures, it was concluded that the binding site for YadA on collagen is determined by a restricted amino acid sequence and is defined within a highly homologous 134-amino acid region. Furthermore, the binding site is not affected by mammalian collagenase digest. Binding of YadA-positive yersiniae to collagen could be inhibited by an antiserum specific for YadA.
Conclusion: This study provides the first evidence of a binding site for bacterial proteins on collagens which is not determined by the repetitive sequence Gly-X-Y of collagens. We speculate that the binding region is conserved between types I and II collagen, the most abundant collagens in the joints. Specific binding of Yersinia products to joint collagens might contribute to the arthritogenic potential of enteropathogenic yersiniae.
Holland-Tummillo K, Shoudy L, Steiner D, Kumar S, Rosa S, Namjoshi P Pathogens. 2020; 9(5).
PMID: 32422907 PMC: 7281241. DOI: 10.3390/pathogens9050375.
Leo J, Elovaara H, Bihan D, Pugh N, Kilpinen S, Raynal N Infect Immun. 2010; 78(7):3226-36.
PMID: 20439473 PMC: 2897373. DOI: 10.1128/IAI.01057-09.
Trimer stability of YadA is critical for virulence of Yersinia enterocolitica.
Schutz M, Weiss E, Schindler M, Hallstrom T, Zipfel P, Linke D Infect Immun. 2010; 78(6):2677-90.
PMID: 20308293 PMC: 2876551. DOI: 10.1128/IAI.01350-09.
Leo J, Elovaara H, Brodsky B, Skurnik M, Goldman A Protein Eng Des Sel. 2008; 21(8):475-84.
PMID: 18467342 PMC: 3254170. DOI: 10.1093/protein/gzn025.
Lacoste M, Tamashiro H, Correa S, de Guzman A, Di Genaro M Rheumatol Int. 2006; 27(7):613-20.
PMID: 17143598 DOI: 10.1007/s00296-006-0274-5.