title: Chaperone-Usher Pili Loci of Colonization Factor-Negative Human EnterotoxigenicEscherichia coli.
abstract: EnterotoxigenicEscherichia coli(ETEC) is one of the most common causes of diarrhea worldwide. Among the 25 different ETEC adhesins, 22 are known as "colonization factors" (CFs), of which 17 are assembled by the chaperone-usher (CU) mechanism. Currently, there is no preventive therapy against ETEC, and CFs have been proposed as components for vaccine development. However, studies of diarrhea-causing ETEC strains worldwide indicate that between 15 and 50% of these are negative for known CFs, hindering the selection of the most widespread structures and suggesting that unknown adhesins remain to be identified. Here, we report the result of a comprehensive analysis of 35 draft genomes of ETEC strains which do not carry known adhesin genes; our goal was to find new CU pili loci. The phylogenetic profiles and serogroups of these strains were highly diverse, a majority of which produced only the heat-labile toxin. We identified 10 pili loci belonging to CU families β (1 locus), γ2(7 loci), κ (1 locus), and π (1 locus), all of which contained the required number of open reading frames (ORFs) to encode functional structures. Three loci were variants of previously-known clusters, three had been only-partially described, and four are novel loci. Intra-loci genetic variability identified would allow the synthesis of up to 14 different structures. Clusters of putative γ2-CU pili were most common (23 strains), followed by putative β-CU pili (12 strains), which have not yet been fully characterized. Overall, our findings significantly increase the number of ETEC adhesion genes associated with human infections.
authors.affiliation: Programa de Microbiología y Micología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile Santiago, Chile.
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.
authors.forename: Miguel
authors.initials: M
authors.lastname: O'Ryan
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: Alexia
authors.initials: A
authors.lastname: Torres
authors.affiliation: 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: Leandro
authors.initials: L
authors.lastname: Cádiz
authors.affiliation: Programa de Microbiología y Micología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de ChileSantiago, Chile; Facultad de Química y Biología, Universidad de Santiago de ChileSantiago, Chile.
authors.forename: Raul
authors.initials: R
authors.lastname: Valdés
authors.affiliation: Programa de Microbiología y Micología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile Santiago, Chile.
authors.forename: Aquiles
authors.initials: A
authors.lastname: Mansilla
authors.affiliation: Programa de Microbiología y Micología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile Santiago, Chile.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Martínez
authors.affiliation: 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: Hernández
authors.affiliation: Programa de Microbiología y Micología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile Santiago, Chile.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Caro
authors.affiliation: Center for Vaccine Development, University of Maryland School of Medicine Baltimore, MD, USA.
authors.forename: Myron M
authors.initials: MM
authors.lastname: Levine
authors.affiliation: Department of Microbiology and Immunology, Institute for Genome Sciences, University of Maryland School of Medicine Baltimore, MD, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Rasko
authors.affiliation: Center for Bioinformatics and Computational Biology, University of Maryland Institute for Advanced Computer Studies College Park, MD, USA.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Hill
authors.affiliation: Center for Bioinformatics and Computational Biology, University of Maryland Institute for Advanced Computer Studies College Park, MD, USA.
authors.forename: Mihai
authors.initials: M
authors.lastname: Pop
authors.affiliation: Department of Epidemiology and Public Health, University of Maryland School of Medicine Baltimore, MD, USA.
authors.forename: O Colin
authors.initials: OC
authors.lastname: Stine
authors.affiliation: Programa de Microbiología y Micología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile Santiago, Chile.
authors.forename: Roberto
authors.initials: R
authors.lastname: Vidal
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics*; D019295:Computational Biology; D054307:Enterotoxigenic Escherichia coli / Q000235:genetics*; D029968:Escherichia coli Proteins / Q000235:genetics*; D010861:Fimbriae, Bacterial / Q000235:genetics*; D056426:Genetic Loci; D016680:Genome, Bacterial; D018832:Molecular Chaperones / Q000235:genetics*
chemical_list: D018829:Adhesins, Bacterial; C574723:CfaC protein, E coli; D029968:Escherichia coli Proteins; D018832:Molecular Chaperones
keywords: ETEC; adhesin; adhesin negative-ETEC; chaperone-usher pili; colonization factors; genome analysis