Allele Variants of Enterotoxigenic Escherichia coli Heat-Labile Toxin Are Globally Transmitted and Associated with Colonization Factors

Handle URI:
http://hdl.handle.net/10754/346764
Title:
Allele Variants of Enterotoxigenic Escherichia coli Heat-Labile Toxin Are Globally Transmitted and Associated with Colonization Factors
Authors:
Joffré, Enrique; von Mentzer, Astrid; Abd El Ghany, Moataz; Oezguen, Numan; Savidge, Tor; Dougan, Gordon; Svennerholm, Ann-Mari; Sjöling, Åsa
Abstract:
Enterotoxigenic Escherichia coli (ETEC) is a significant cause of morbidity and mortality in the developing world. ETEC-mediated diarrhea is orchestrated by heat-labile toxin (LT) and heat-stable toxins (STp and STh), acting in concert with a repertoire of more than 25 colonization factors (CFs). LT, the major virulence factor, induces fluid secretion after delivery of a monomeric ADP-ribosylase (LTA) and its pentameric carrier B subunit (LTB). A study of ETEC isolates from humans in Brazil reported the existence of natural LT variants. In the present study, analysis of predicted amino acid sequences showed that the LT amino acid polymorphisms are associated with a geographically and temporally diverse set of 192 clinical ETEC strains and identified 12 novel LT variants. Twenty distinct LT amino acid variants were observed in the globally distributed strains, and phylogenetic analysis showed these to be associated with different CF profiles. Notably, the most prevalent LT1 allele variants were correlated with major ETEC lineages expressing CS1 + CS3 or CS2 + CS3, and the most prevalent LT2 allele variants were correlated with major ETEC lineages expressing CS5 + CS6 or CFA/I. LTB allele variants generally exhibited more-stringent amino acid sequence conservation (2 substitutions identified) than LTA allele variants (22 substitutions identified). The functional impact of LT1 and LT2 polymorphisms on virulence was investigated by measuring total-toxin production, secretion, and stability using GM1-enzyme-linked immunosorbent assays (GM1-ELISA) and in silico protein modeling. Our data show that LT2 strains produce 5-fold more toxin than LT1 strains (P < 0.001), which may suggest greater virulence potential for this genetic variant. Our data suggest that functionally distinct LT-CF variants with increased fitness have persisted during the evolution of ETEC and have spread globally.
KAUST Department:
Pathogen Genomics Laboratory; Computational Bioscience Research Center (CBRC)
Citation:
Allele Variants of Enterotoxigenic Escherichia coli Heat-Labile Toxin Are Globally Transmitted and Associated with Colonization Factors 2015, 197 (2):392 Journal of Bacteriology
Publisher:
American Society for Microbiology
Journal:
Journal of Bacteriology
Issue Date:
15-Jan-2015
DOI:
10.1128/JB.02050-14
PubMed ID:
25404692
PubMed Central ID:
PMC4272596
Type:
Article
ISSN:
0021-9193; 1098-5530
Additional Links:
http://jb.asm.org/lookup/doi/10.1128/JB.02050-14
Appears in Collections:
Articles; Computational Bioscience Research Center (CBRC)

Full metadata record

DC FieldValue Language
dc.contributor.authorJoffré, Enriqueen
dc.contributor.authorvon Mentzer, Astriden
dc.contributor.authorAbd El Ghany, Moatazen
dc.contributor.authorOezguen, Numanen
dc.contributor.authorSavidge, Toren
dc.contributor.authorDougan, Gordonen
dc.contributor.authorSvennerholm, Ann-Marien
dc.contributor.authorSjöling, Åsaen
dc.date.accessioned2015-03-17T13:18:44Zen
dc.date.available2015-03-17T13:18:44Zen
dc.date.issued2015-01-15en
dc.identifier.citationAllele Variants of Enterotoxigenic Escherichia coli Heat-Labile Toxin Are Globally Transmitted and Associated with Colonization Factors 2015, 197 (2):392 Journal of Bacteriologyen
dc.identifier.issn0021-9193en
dc.identifier.issn1098-5530en
dc.identifier.pmid25404692en
dc.identifier.doi10.1128/JB.02050-14en
dc.identifier.urihttp://hdl.handle.net/10754/346764en
dc.description.abstractEnterotoxigenic Escherichia coli (ETEC) is a significant cause of morbidity and mortality in the developing world. ETEC-mediated diarrhea is orchestrated by heat-labile toxin (LT) and heat-stable toxins (STp and STh), acting in concert with a repertoire of more than 25 colonization factors (CFs). LT, the major virulence factor, induces fluid secretion after delivery of a monomeric ADP-ribosylase (LTA) and its pentameric carrier B subunit (LTB). A study of ETEC isolates from humans in Brazil reported the existence of natural LT variants. In the present study, analysis of predicted amino acid sequences showed that the LT amino acid polymorphisms are associated with a geographically and temporally diverse set of 192 clinical ETEC strains and identified 12 novel LT variants. Twenty distinct LT amino acid variants were observed in the globally distributed strains, and phylogenetic analysis showed these to be associated with different CF profiles. Notably, the most prevalent LT1 allele variants were correlated with major ETEC lineages expressing CS1 + CS3 or CS2 + CS3, and the most prevalent LT2 allele variants were correlated with major ETEC lineages expressing CS5 + CS6 or CFA/I. LTB allele variants generally exhibited more-stringent amino acid sequence conservation (2 substitutions identified) than LTA allele variants (22 substitutions identified). The functional impact of LT1 and LT2 polymorphisms on virulence was investigated by measuring total-toxin production, secretion, and stability using GM1-enzyme-linked immunosorbent assays (GM1-ELISA) and in silico protein modeling. Our data show that LT2 strains produce 5-fold more toxin than LT1 strains (P < 0.001), which may suggest greater virulence potential for this genetic variant. Our data suggest that functionally distinct LT-CF variants with increased fitness have persisted during the evolution of ETEC and have spread globally.en
dc.publisherAmerican Society for Microbiologyen
dc.relation.urlhttp://jb.asm.org/lookup/doi/10.1128/JB.02050-14en
dc.rightsArchived with thanks to Journal of Bacteriology. Copyright © 2015, American Society for Microbiology. All Rights Reserved. doi:10.1128/JB.02050-14en
dc.titleAllele Variants of Enterotoxigenic Escherichia coli Heat-Labile Toxin Are Globally Transmitted and Associated with Colonization Factorsen
dc.typeArticleen
dc.contributor.departmentPathogen Genomics Laboratoryen
dc.contributor.departmentComputational Bioscience Research Center (CBRC)en
dc.identifier.journalJournal of Bacteriologyen
dc.identifier.pmcidPMC4272596en
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionDepartment of Microbiology and Immunology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Swedenen
dc.contributor.institutionInstitute of Molecular Biology and Biotechnology, Universidad Mayor de San Andrés, La Paz, Boliviaen
dc.contributor.institutionThe Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdomen
dc.contributor.institutionTexas Children's Microbiome Center, Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USAen
dc.contributor.institutionDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Swedenen
dc.contributor.affiliationKing Abdullah University of Science and Technology (KAUST)en
kaust.authorAbd El Ghany, Moatazen
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