title: CesAB is an enteropathogenic Escherichia coli chaperone for the type-III translocator proteins EspA and EspB.
abstract: Enteropathogenic Escherichia coli (EPEC) are extracellular pathogens that colonize mucosal surfaces of the intestine via formation of attaching and effacing (A/E) lesions. The genes responsible for induction of the A/E lesions are located on a pathogenicity island, termed the locus of enterocyte effacement (LEE), which encodes the adhesin intimin and the type III secretion system needle complex, translocator and effector proteins. One of the major EPEC translocator proteins, EspA, forms a filamentous conduit along which secreted proteins travel before they arrive at the translocation pore in the plasma membrane of the host cell, which is composed of EspB and EspD. Prior to secretion, many type III proteins, including translocators, are maintained in the bacterial cytoplasm by association with a specific chaperone. In EPEC, chaperones have been identified for the effector proteins Tir, Map and EspF, and the translocator proteins EspD and EspB. In this study, CesAB (Orf3 of the LEE) was identified as a chaperone for EspA and EspB. Specific CesAB-EspA and CesAB-EspB protein interactions are demonstrated. CesAB was essential for stability of EspA within the bacterial cell prior to secretion. Furthermore, a cesAB mutant failed to secrete EspA, as well as EspB, to assemble EspA filaments, to induce A/E lesion following infection of HEp-2 cells and to adhere to, or cause haemolysis of, erythrocytes.
authors.affiliation: Centre for Molecular Microbiology and Infection, Department of Biological Sciences, Imperial College, London SW7 2AZ.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Creasey
authors.affiliation: Departments of Molecular Genetics and Biotechnology, The Hebrew University, Faculty of Medicine, POB 12272, Jerusalem 91120, Israel.
authors.forename: Devorah
authors.initials: D
authors.lastname: Friedberg
authors.affiliation: Institute of Child Health, University of Birmingham, Birmingham B4 6NH, UK.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Shaw
authors.affiliation: Departments of Molecular Genetics and Biotechnology, The Hebrew University, Faculty of Medicine, POB 12272, Jerusalem 91120, Israel.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Umanski
authors.affiliation: Institute of Child Health, University of Birmingham, Birmingham B4 6NH, UK.
authors.forename: Stuart
authors.initials: S
authors.lastname: Knutton
authors.affiliation: Departments of Molecular Genetics and Biotechnology, The Hebrew University, Faculty of Medicine, POB 12272, Jerusalem 91120, Israel.
authors.forename: Ilan
authors.initials: I
authors.lastname: Rosenshine
authors.affiliation: Centre for Molecular Microbiology and Infection, Department of Biological Sciences, Imperial College, London SW7 2AZ.
authors.forename: Gad
authors.initials: G
authors.lastname: Frankel
mesh_terms: D001422:Bacterial Adhesion / Q000235:genetics; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics*; D001483:Base Sequence; D004269:DNA, Bacterial / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics* / Q000472:pathogenicity*; D029968:Escherichia coli Proteins / Q000235:genetics*; D005798:Genes, Bacterial; D018832:Molecular Chaperones / Q000235:genetics*; D009154:Mutation; D016366:Open Reading Frames; D009876:Operon; D014158:Transcription, Genetic; D014774:Virulence / Q000235:genetics
chemical_list: D001425:Bacterial Outer Membrane Proteins; D004269:DNA, Bacterial; C087863:EaeB protein, E coli; D029968:Escherichia coli Proteins; C102051:EspA protein, E coli; D018832:Molecular Chaperones