title: Bacterial Factors Associated with Lethal Outcome of Enteropathogenic Escherichia coli Infection: Genomic Case-Control Studies.
abstract: BACKGROUND
  Typical enteropathogenic Escherichia coli (tEPEC) strains were associated with mortality in the Global Enteric Multicenter Study (GEMS). Genetic differences in tEPEC strains could underlie some of the variability in clinical outcome.
  
  
  METHODS
  We produced draft genome sequences of all available tEPEC strains from GEMS lethal infections (LIs) and of closely matched EPEC strains from GEMS subjects with non-lethal symptomatic infections (NSIs) and asymptomatic infections (AIs) to identify gene clusters (potential protein encoding sequences sharing ≥90% nucleotide sequence identity) associated with lethality.
  
  
  RESULTS
  Among 14,412 gene clusters identified, the presence or absence of 392 was associated with clinical outcome. As expected, more gene clusters were associated with LI versus AI than LI versus NSI. The gene clusters more prevalent in strains from LI than those from NSI and AI included those encoding proteins involved in O-antigen biogenesis, while clusters encoding type 3 secretion effectors EspJ and OspB were among those more prevalent in strains from non-lethal infections. One gene cluster encoding a variant of an NleG ubiquitin ligase was associated with LI versus AI, while two other nleG clusters had the opposite association. Similar associations were found for two nleG gene clusters in an additional, larger sample of NSI and AI GEMS strains.
  
  
  CONCLUSIONS
  Particular genes are associated with lethal tEPEC infections. Further study of these factors holds potential to unravel the mechanisms underlying severe disease and to prevent adverse outcomes.
authors.affiliation: Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Donnenberg
authors.affiliation: Institute for Genome Sciences, Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Tracy H
authors.initials: TH
authors.lastname: Hazen
authors.affiliation: Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Tamer H
authors.initials: TH
authors.lastname: Farag
authors.affiliation: Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Sandra
authors.initials: S
authors.lastname: Panchalingam
authors.affiliation: Medical Research Council, Fajara, The Gambia.
authors.forename: Martin
authors.initials: M
authors.lastname: Antonio
authors.affiliation: International Center for Diarrhoeal Disease Research, Dhaka, Bangladesh.
authors.forename: Anowar
authors.initials: A
authors.lastname: Hossain
authors.affiliation: Centro de Investigacao em Saude de Manhica, Maputo, Mozambique.
authors.forename: Inacio
authors.initials: I
authors.lastname: Mandomando
authors.affiliation: Kenya Medical Research Institute/Center for Disease Control, Kisumu, Kenya.
authors.forename: John Benjamin
authors.initials: JB
authors.lastname: Ochieng
authors.affiliation: National Institute of Cholera and Enteric Diseases, Kolkata, India.
authors.forename: Thandavarayan
authors.initials: T
authors.lastname: Ramamurthy
authors.affiliation: Center for Vaccine Development-Mali, Bamako, Mali.
authors.forename: Boubou
authors.initials: B
authors.lastname: Tamboura
authors.affiliation: The Aga Khan University, Karachi, Pakistan.
authors.forename: Anita
authors.initials: A
authors.lastname: Zaidi
authors.affiliation: Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Myron M
authors.initials: MM
authors.lastname: Levine
authors.affiliation: Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Karen
authors.initials: K
authors.lastname: Kotloff
authors.affiliation: Institute for Genome Sciences, Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: David A
authors.initials: DA
authors.lastname: Rasko
authors.affiliation: Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Virginia, United States of America.
authors.forename: James P
authors.initials: JP
authors.lastname: Nataro
mesh_terms: D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D054308:Enteropathogenic Escherichia coli / Q000235:genetics*; D004927:Escherichia coli Infections / Q000401:mortality*; D029968:Escherichia coli Proteins / Q000235:genetics; D005798:Genes, Bacterial; D023281:Genomics; D006801:Humans; D007223:Infant; D005810:Multigene Family; D019081:O Antigens / Q000235:genetics
chemical_list: D029968:Escherichia coli Proteins; D019081:O Antigens