title: Evolution of atypical enteropathogenic E. coli by repeated acquisition of LEE pathogenicity island variants.
abstract: Atypical enteropathogenic Escherichia coli (aEPEC) is an umbrella term given to E. coli that possess a type III secretion system encoded in the locus of enterocyte effacement (LEE), but lack the virulence factors (stx, bfpA) that characterize enterohaemorrhagic E. coli and typical EPEC, respectively. The burden of disease caused by aEPEC has recently increased in industrialized and developing nations, yet the population structure and virulence profile of this emerging pathogen are poorly understood. Here, we generated whole-genome sequences of 185 aEPEC isolates collected during the Global Enteric Multicenter Study from seven study sites in Asia and Africa, and compared them with publicly available E. coli genomes. Phylogenomic analysis revealed ten distinct widely distributed aEPEC clones. Analysis of genetic variation in the LEE pathogenicity island identified 30 distinct LEE subtypes divided into three major lineages. Each LEE lineage demonstrated a preferred chromosomal insertion site and different complements of non-LEE encoded effector genes, indicating distinct patterns of evolution of these lineages. This study provides the first detailed genomic framework for aEPEC in the context of the EPEC pathotype and will facilitate further studies into the epidemiology and pathogenicity of EPEC by enabling the detection and tracking of specific clones and LEE variants.
authors: Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Victoria 3010, Australia.|Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Victoria 3010, Australia.|Centre for Systems Genomics, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors: Danielle J
authors: DJ
authors: Ingle
authors: Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Victoria 3010, Australia.
authors: Marija
authors: M
authors: Tauschek
authors: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Victoria 3010, Australia.|Centre for Systems Genomics, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors: David J
authors: DJ
authors: Edwards
authors: Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Victoria 3010, Australia.
authors: Dianna M
authors: DM
authors: Hocking
authors: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
authors: Derek J
authors: DJ
authors: Pickard
authors: Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Victoria 3010, Australia.
authors: Kristy I
authors: KI
authors: Azzopardi
authors: Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Victoria 3010, Australia.
authors: Thakshila
authors: T
authors: Amarasena
authors: Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Victoria 3010, Australia.
authors: Vicki
authors: V
authors: Bennett-Wood
authors: Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Victoria 3010, Australia.
authors: Jaclyn S
authors: JS
authors: Pearson
authors: Centre pour le Développement des Vaccins du Mali, Bamako, Mali.
authors: Boubou
authors: B
authors: Tamboura
authors: Medical Research Council Unit (United Kingdom), Fajara, The Gambia.
authors: Martin
authors: M
authors: Antonio
authors: Kenya Medical Research Institute/Centers for Disease Control and Prevention, Kisumu, Kenya.
authors: John B
authors: JB
authors: Ochieng
authors: Kenya Medical Research Institute/Centers for Disease Control and Prevention, Kisumu, Kenya.
authors: Joseph
authors: J
authors: Oundo
authors: Centro de Investigação em Saúde de Manhiça, (CISM), CP 1929, Maputo, Mozambique.|Instituto Nacional de Saúde, Ministério da Saúde, Maputo, Mozambique.
authors: Inácio
authors: I
authors: Mandomando
authors: Department of Paediatrics and Child Health, The Aga Khan University, Karachi 74800, Pakistan.
authors: Shahida
authors: S
authors: Qureshi
authors: National Institute of Cholera and Enteric Diseases, Kolkata, West Bengal 700010, India.
authors: Thandavarayan
authors: T
authors: Ramamurthy
authors: International Centre for Diarrhoeal Disease Research, Mohakhali, Dhaka, Bangladesh.
authors: Anowar
authors: A
authors: Hossain
authors: Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
authors: Karen L
authors: KL
authors: Kotloff
authors: Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.
authors: James P
authors: JP
authors: Nataro
authors: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
authors: Gordon
authors: G
authors: Dougan
authors: Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
authors: Myron M
authors: MM
authors: Levine
authors: Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Victoria 3010, Australia.|Murdoch Childrens Research Institute, Royal Children's Hospital, Victoria 3052, Australia.
authors: Roy M
authors: RM
authors: Robins-Browne
authors: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Victoria 3010, Australia.|Centre for Systems Genomics, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors: Kathryn E
authors: http://orcid.org/0000-0003-3949-2471
authors: KE
authors: Holt
mesh_terms: D000349:Africa / Q000453:epidemiology; D001208:Asia / Q000453:epidemiology; D054308:Enteropathogenic Escherichia coli / Q000145:classification* / Q000235:genetics*; D004927:Escherichia coli Infections / Q000453:epidemiology / Q000382:microbiology; D029968:Escherichia coli Proteins / Q000235:genetics*; D019143:Evolution, Molecular; D014644:Genetic Variation; D016680:Genome, Bacterial; D044404:Genomic Islands; D005838:Genotype; D010750:Phosphoproteins / Q000235:genetics*; D010802:Phylogeny; D017422:Sequence Analysis, DNA
chemical_list: D029968:Escherichia coli Proteins; C457340:LEE protein, E coli; D010750:Phosphoproteins