title: A novel dispersin protein in enteroaggregative Escherichia coli.
abstract: Enteroaggregative Escherichia coli (EAEC) is a diarrheal pathogen defined by its characteristic aggregative adherence (AA) to HEp-2 cells in culture. We have previously shown that EAEC strains secrete a 10-kDa protein that is immunogenic in a human EAEC challenge model. We report here that this protein is encoded by a gene (called aap) lying immediately upstream of that encoding the AggR transcriptional activator, and that aap is under AggR control. The product of aap has a typical signal sequence and is secreted to the extracellular milieu, where it remains noncovalently attached to the surface of the bacterium. EAEC aap mutants aggregate more intensely than the wild-type parent in a number of assays, forming larger aggregates and fewer individual bacteria. Infection of colonic biopsies with wild-type EAEC strain 042 and its aap mutant revealed more dramatic autoagglutination of the mutant compared with the wild-type parent. Our data suggest that the aap gene product participates in formation of a surface coat that acts to disperse the bacteria, thus partially counteracting aggregation mediated by aggregative adherence fimbriae. We have therefore named the aap gene product "dispersin," and we propose that it may be representative of a functional class of colonization factors. Since dispersin is expressed in vivo, is highly immunogenic, and is present in most EAEC strains, it holds considerable promise as an EAEC immunogen.
authors.affiliation: Center for Vaccine Development, Department of Pediatrics, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: Jalaluddin
authors.initials: J
authors.lastname: Sheikh
authors.forename: John R
authors.initials: JR
authors.lastname: Czeczulin
authors.forename: Susan
authors.initials: S
authors.lastname: Harrington
authors.forename: Susan
authors.initials: S
authors.lastname: Hicks
authors.forename: Ian R
authors.initials: IR
authors.lastname: Henderson
authors.forename: Chantal
authors.initials: C
authors.lastname: Le Bouguénec
authors.forename: Pierre
authors.initials: P
authors.lastname: Gounon
authors.forename: Alan
authors.initials: A
authors.lastname: Phillips
authors.forename: James P
authors.initials: JP
authors.lastname: Nataro
mesh_terms: D000371:Agglutination; D001422:Bacterial Adhesion; D002874:Chromosome Mapping; D029968:Escherichia coli Proteins / Q000032:analysis* / Q000235:genetics / Q000502:physiology; D008854:Microscopy, Electron; D015534:Trans-Activators / Q000502:physiology; D014158:Transcription, Genetic
chemical_list: C088603:AggR protein, E coli; D029968:Escherichia coli Proteins; D015534:Trans-Activators