Show simple item record

dc.contributor.authorJoffré, Enrique
dc.contributor.authorvon Mentzer, Astrid
dc.contributor.authorAbd El Ghany, Moataz
dc.contributor.authorOezguen, Numan
dc.contributor.authorSavidge, Tor
dc.contributor.authorDougan, Gordon
dc.contributor.authorSvennerholm, Ann-Mari
dc.contributor.authorSjöling, Åsa
dc.date.accessioned2015-03-17T13:18:44Z
dc.date.available2015-03-17T13:18:44Z
dc.date.issued2015-01-15
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 Bacteriology
dc.identifier.issn0021-9193
dc.identifier.issn1098-5530
dc.identifier.pmid25404692
dc.identifier.doi10.1128/JB.02050-14
dc.identifier.urihttp://hdl.handle.net/10754/346764
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.
dc.publisherAmerican Society for Microbiology
dc.relation.urlhttp://jb.asm.org/lookup/doi/10.1128/JB.02050-14
dc.rightsArchived with thanks to Journal of Bacteriology. Copyright © 2015, American Society for Microbiology. All Rights Reserved. doi:10.1128/JB.02050-14
dc.titleAllele Variants of Enterotoxigenic Escherichia coli Heat-Labile Toxin Are Globally Transmitted and Associated with Colonization Factors
dc.typeArticle
dc.contributor.departmentPathogen Genomics Laboratory
dc.contributor.departmentComputational Bioscience Research Center (CBRC)
dc.identifier.journalJournal of Bacteriology
dc.identifier.pmcidPMC4272596
dc.eprint.versionPublisher's Version/PDF
dc.contributor.institutionDepartment of Microbiology and Immunology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
dc.contributor.institutionInstitute of Molecular Biology and Biotechnology, Universidad Mayor de San Andrés, La Paz, Bolivia
dc.contributor.institutionThe Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom
dc.contributor.institutionTexas Children's Microbiome Center, Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA
dc.contributor.institutionDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
dc.contributor.affiliationKing Abdullah University of Science and Technology (KAUST)
kaust.personAbd El Ghany, Moataz
refterms.dateFOA2018-06-13T10:47:24Z


Files in this item

Thumbnail
Name:
J. Bacteriol.-2015-Joffré-392-403.pdf
Size:
2.022Mb
Format:
PDF
Description:
Main article
Thumbnail
Name:
zjb999093448so1.pdf
Size:
1.048Mb
Format:
PDF
Description:
Supplemental file

This item appears in the following Collection(s)

Show simple item record