title: TleA, a Tsh-like autotransporter identified in a human enterotoxigenic Escherichia coli strain.
abstract: Enterotoxigenic Escherichia coli (ETEC), a leading cause of acute diarrhea, colonizes the intestine by means of adhesins. However, 15 to 50% of clinical isolates are negative for known adhesins, making it difficult to identify antigens for broad-coverage vaccines. The ETEC strain 1766a, obtained from a child with watery diarrhea in Chile, harbors the colonization factor CS23 but is negative for other known adhesins. One clone, derived from an ETEC 1766a genomic library (clone G10), did not produce CS23 yet was capable of adhering to Caco-2 cells. The goal of this study was to identify the gene responsible for this capacity. Random transposon-based mutagenesis allowed the identification of a 4,110-bp gene that codes for a homologue of the temperature-sensitive hemagglutinin (Tsh) autotransporter described in avian E. coli strains (97% identity, 90% coverage) and that is called TleA (Tsh-like ETEC autotransporter) herein. An isogenic ETEC 1766a strain with a tleA mutation showed an adhesion level similar to that of the wild-type strain, suggesting that the gene does not direct attachment to Caco-2 cells. However, expression of tleA conferred the capacity for adherence to nonadherent E. coli HB101. This effect coincided with the detection of TleA on the surface of nonpermeabilized bacteria, while, conversely, ETEC 1766a seems to secrete most of the produced autotransporter to the medium. On the other hand, TleA was capable of degrading bovine submaxillary mucin and leukocyte surface glycoproteins CD45 and P-selectin glycoprotein ligand 1 (PSGL-1). These results suggest that TleA promotes colonization of the intestinal epithelium and that it may modulate the host immune response.
authors.affiliation: Departamento de Biología, Facultad de Química y Biología, Universidad de Santiago de Chile, Santiago, Chile Programa de Microbiología y Micología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
authors.forename: Daniela
authors.initials: D
authors.lastname: Gutiérrez
authors.affiliation: Programa de Microbiología y Micología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
authors.forename: Mirka
authors.initials: M
authors.lastname: Pardo
authors.affiliation: Programa de Microbiología y Micología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
authors.forename: David
authors.initials: D
authors.lastname: Montero
authors.affiliation: Departamento de Microbiología, Facultad de Ciencias Biológicas, Universidad de Concepción, Concepción, Chile.
authors.forename: Angel
authors.initials: A
authors.lastname: Oñate
authors.affiliation: Centro de Estudios Moleculares, Departamento de Pediatría, Hospital Dr. Luis Calvo Mackenna, Universidad de Chile, Santiago, Chile.
authors.forename: Mauricio J
authors.initials: MJ
authors.lastname: Farfán
authors.affiliation: Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Virginia, USA.
authors.forename: Fernando
authors.initials: F
authors.lastname: Ruiz-Pérez
authors.affiliation: Programa de Microbiología y Micología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile felipedelcanto@med.uchile.cl rvidal@med.uchile.cl.
authors.forename: Felipe
authors.initials: F
authors.lastname: Del Canto
authors.affiliation: Programa de Microbiología y Micología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile felipedelcanto@med.uchile.cl rvidal@med.uchile.cl.
authors.forename: Roberto
authors.initials: R
authors.lastname: Vidal
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics* / Q000378:metabolism; D018830:Adhesins, Escherichia coli / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001422:Bacterial Adhesion; D018938:Caco-2 Cells; D002675:Child, Preschool; D002677:Chile; D004251:DNA Transposable Elements; D003967:Diarrhea / Q000382:microbiology; D054307:Enterotoxigenic Escherichia coli / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology*; D004847:Epithelial Cells / Q000382:microbiology*; D004927:Escherichia coli Infections / Q000382:microbiology; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000378:metabolism; D017353:Gene Deletion; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016254:Mutagenesis, Insertional
chemical_list: D018829:Adhesins, Bacterial; D018830:Adhesins, Escherichia coli; D004251:DNA Transposable Elements; D029968:Escherichia coli Proteins; C000598982:TleA protein, E coli; C112027:tsh protein, E coli