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Mutagenesis of conserved tryptophan residues within the receptor-binding domain of intimin: influence on binding activity and virulence

Reece, S; Simmons, CP; Fitzhenry, RJ; Batchelor, M; Hale, C; Matthews, S; ... Frankel, G; + view all (2002) Mutagenesis of conserved tryptophan residues within the receptor-binding domain of intimin: influence on binding activity and virulence. Microbiology-Sgm , 148 (3) 657 - 665.

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Abstract

Intimate bacterial adhesion to intestinal epithelium is a pathogenic mechanism shared by several human and animal enteric pathogens, including enteropathogenic and enterohaemorrhagic Escherichia coli and Citrobacter rodentium. The proteins directly involved in this process are the outermembrane adhesion molecule intimin and the translocated intimin receptor, Tir. The receptor-binding activity of intimin resides within the carboxy terminus 280 aa (Int280) of the polypeptide. Four tryptophan residues, W117/776, W136/795, W222/881 and W240/899, are conserved within different Int280 molecules that otherwise show considerable sequence variation. In this study the influence of site-directed mutagenesis of each of the four tryptophan residues on intimin-Tir interactions and on intimin- mediated intimate attachment was determined. The mutant intimins were also studied using a variety of in vitro and in vivo infection models. The results show that all the substitutions modulated intimin activity, although some mutations had more profound effects than others

Type:Article
Title:Mutagenesis of conserved tryptophan residues within the receptor-binding domain of intimin: influence on binding activity and virulence
Additional information:Journal English Article SOC GENERAL MICROBIOLOGY MAR 529YB READING MICROBIOLOGY-SGM MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AE, BERKS, ENGLAND
Keywords:activity, Adhesion, adhesion molecule, Animal, attachment, BACTERIAL, Bacterial Adhesion, Bacterial-adhesion, BINDING, Citrobacter rodentium, CITROBACTER-FREUNDII BIOTYPE, domain, EAE GENE, effects, EHEC, English, enterohaemorrhagic, enteropathogenic, ENTEROPATHOGENIC ESCHERICHIA-COLI, EPEC, EPITHELIA, Epithelium, Escherichia coli, ESCHERICHIA-COLI, HOST-CELLS, IDENTIFICATION, in vitro, in vivo, In-vitro, in-vivo, Infection, interaction, intestinal, INTESTINAL EPITHELIUM, intimin, LOCUS, MECHANISM, microbiology, model, MODELS, Molecule, MOLECULES, MURINE COLONIC HYPERPLASIA, Mutagenesis, Mutant, Mutation, MUTATIONS, Other, Pathogen, PATHOGENS, polypeptide, process, processes, PROTEIN, Proteins, RD, Reading, Receptor, Result, SEQUENCE, site-directed mutagenesis, STRUCTURAL BASIS, SUBSTITUTION, Tir, TISSUE-CULTURE CELLS, Tryptophan, Virulence, VITRO, vivo
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Child Health

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