Bacterial Factors Associated with Lethal Outcome of Enteropathogenic Escherichia coli Infection: Genomic Case-Control Studies.
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 avail...
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ftdoajarticles:oai:doaj.org/article:2d5dafe608ed4f4596f33da3473eef4b 2023-05-15T15:09:41+02:00 Bacterial Factors Associated with Lethal Outcome of Enteropathogenic Escherichia coli Infection: Genomic Case-Control Studies. Michael S Donnenberg Tracy H Hazen Tamer H Farag Sandra Panchalingam Martin Antonio Anowar Hossain Inacio Mandomando John Benjamin Ochieng Thandavarayan Ramamurthy Boubou Tamboura Anita Zaidi Myron M Levine Karen Kotloff David A Rasko James P Nataro 2015-05-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0003791 https://doaj.org/article/2d5dafe608ed4f4596f33da3473eef4b EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC4433268?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0003791 https://doaj.org/article/2d5dafe608ed4f4596f33da3473eef4b PLoS Neglected Tropical Diseases, Vol 9, Iss 5, p e0003791 (2015) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2015 ftdoajarticles https://doi.org/10.1371/journal.pntd.0003791 2022-12-30T21:59:59Z 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. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 9 5 e0003791 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Michael S Donnenberg Tracy H Hazen Tamer H Farag Sandra Panchalingam Martin Antonio Anowar Hossain Inacio Mandomando John Benjamin Ochieng Thandavarayan Ramamurthy Boubou Tamboura Anita Zaidi Myron M Levine Karen Kotloff David A Rasko James P Nataro Bacterial Factors Associated with Lethal Outcome of Enteropathogenic Escherichia coli Infection: Genomic Case-Control Studies. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
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. |
format |
Article in Journal/Newspaper |
author |
Michael S Donnenberg Tracy H Hazen Tamer H Farag Sandra Panchalingam Martin Antonio Anowar Hossain Inacio Mandomando John Benjamin Ochieng Thandavarayan Ramamurthy Boubou Tamboura Anita Zaidi Myron M Levine Karen Kotloff David A Rasko James P Nataro |
author_facet |
Michael S Donnenberg Tracy H Hazen Tamer H Farag Sandra Panchalingam Martin Antonio Anowar Hossain Inacio Mandomando John Benjamin Ochieng Thandavarayan Ramamurthy Boubou Tamboura Anita Zaidi Myron M Levine Karen Kotloff David A Rasko James P Nataro |
author_sort |
Michael S Donnenberg |
title |
Bacterial Factors Associated with Lethal Outcome of Enteropathogenic Escherichia coli Infection: Genomic Case-Control Studies. |
title_short |
Bacterial Factors Associated with Lethal Outcome of Enteropathogenic Escherichia coli Infection: Genomic Case-Control Studies. |
title_full |
Bacterial Factors Associated with Lethal Outcome of Enteropathogenic Escherichia coli Infection: Genomic Case-Control Studies. |
title_fullStr |
Bacterial Factors Associated with Lethal Outcome of Enteropathogenic Escherichia coli Infection: Genomic Case-Control Studies. |
title_full_unstemmed |
Bacterial Factors Associated with Lethal Outcome of Enteropathogenic Escherichia coli Infection: Genomic Case-Control Studies. |
title_sort |
bacterial factors associated with lethal outcome of enteropathogenic escherichia coli infection: genomic case-control studies. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2015 |
url |
https://doi.org/10.1371/journal.pntd.0003791 https://doaj.org/article/2d5dafe608ed4f4596f33da3473eef4b |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 9, Iss 5, p e0003791 (2015) |
op_relation |
http://europepmc.org/articles/PMC4433268?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0003791 https://doaj.org/article/2d5dafe608ed4f4596f33da3473eef4b |
op_doi |
https://doi.org/10.1371/journal.pntd.0003791 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
9 |
container_issue |
5 |
container_start_page |
e0003791 |
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1766340825773506560 |