Conservation and global distribution of non-canonical antigens in Enterotoxigenic Escherichia coli.
Background Enterotoxigenic Escherichia coli (ETEC) cause significant diarrheal morbidity and mortality in children of resource-limited regions, warranting development of effective vaccine strategies. Genetic diversity of the ETEC pathovar has impeded development of broadly protective vaccines center...
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ftdoajarticles:oai:doaj.org/article:a808e145e78f402ea679a8910db41b1f 2023-05-15T15:08:28+02:00 Conservation and global distribution of non-canonical antigens in Enterotoxigenic Escherichia coli. F Matthew Kuhlmann John Martin Tracy H Hazen Tim J Vickers Madeline Pashos Pablo C Okhuysen Oscar G Gómez-Duarte Elizabeth Cebelinski Dave Boxrud Felipe Del Canto Roberto Vidal Firdausi Qadri Makedonka Mitreva David A Rasko James M Fleckenstein 2019-11-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0007825 https://doaj.org/article/a808e145e78f402ea679a8910db41b1f EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0007825 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0007825 https://doaj.org/article/a808e145e78f402ea679a8910db41b1f PLoS Neglected Tropical Diseases, Vol 13, Iss 11, p e0007825 (2019) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2019 ftdoajarticles https://doi.org/10.1371/journal.pntd.0007825 2022-12-31T13:48:05Z Background Enterotoxigenic Escherichia coli (ETEC) cause significant diarrheal morbidity and mortality in children of resource-limited regions, warranting development of effective vaccine strategies. Genetic diversity of the ETEC pathovar has impeded development of broadly protective vaccines centered on the classical canonical antigens, the colonization factors and heat-labile toxin. Two non-canonical ETEC antigens, the EtpA adhesin, and the EatA mucinase are immunogenic in humans and protective in animal models. To foster rational vaccine design that complements existing strategies, we examined the distribution and molecular conservation of these antigens in a diverse population of ETEC isolates. Methods Geographically diverse ETEC isolates (n = 1159) were interrogated by PCR, immunoblotting, and/or whole genome sequencing (n = 46) to examine antigen conservation. The most divergent proteins were purified and their core functions assessed in vitro. Results EatA and EtpA or their coding sequences were present in 57.0% and 51.5% of the ETEC isolates overall, respectively; and were globally dispersed without significant regional differences in antigen distribution. These antigens also exhibited >93% amino acid sequence identity with even the most divergent proteins retaining the core adhesin and mucinase activity assigned to the prototype molecules. Conclusions EtpA and EatA are well-conserved molecules in the ETEC pathovar, suggesting that they serve important roles in virulence and that they could be exploited for rational vaccine design. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 13 11 e0007825 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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English |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 F Matthew Kuhlmann John Martin Tracy H Hazen Tim J Vickers Madeline Pashos Pablo C Okhuysen Oscar G Gómez-Duarte Elizabeth Cebelinski Dave Boxrud Felipe Del Canto Roberto Vidal Firdausi Qadri Makedonka Mitreva David A Rasko James M Fleckenstein Conservation and global distribution of non-canonical antigens in Enterotoxigenic Escherichia coli. |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Background Enterotoxigenic Escherichia coli (ETEC) cause significant diarrheal morbidity and mortality in children of resource-limited regions, warranting development of effective vaccine strategies. Genetic diversity of the ETEC pathovar has impeded development of broadly protective vaccines centered on the classical canonical antigens, the colonization factors and heat-labile toxin. Two non-canonical ETEC antigens, the EtpA adhesin, and the EatA mucinase are immunogenic in humans and protective in animal models. To foster rational vaccine design that complements existing strategies, we examined the distribution and molecular conservation of these antigens in a diverse population of ETEC isolates. Methods Geographically diverse ETEC isolates (n = 1159) were interrogated by PCR, immunoblotting, and/or whole genome sequencing (n = 46) to examine antigen conservation. The most divergent proteins were purified and their core functions assessed in vitro. Results EatA and EtpA or their coding sequences were present in 57.0% and 51.5% of the ETEC isolates overall, respectively; and were globally dispersed without significant regional differences in antigen distribution. These antigens also exhibited >93% amino acid sequence identity with even the most divergent proteins retaining the core adhesin and mucinase activity assigned to the prototype molecules. Conclusions EtpA and EatA are well-conserved molecules in the ETEC pathovar, suggesting that they serve important roles in virulence and that they could be exploited for rational vaccine design. |
format |
Article in Journal/Newspaper |
author |
F Matthew Kuhlmann John Martin Tracy H Hazen Tim J Vickers Madeline Pashos Pablo C Okhuysen Oscar G Gómez-Duarte Elizabeth Cebelinski Dave Boxrud Felipe Del Canto Roberto Vidal Firdausi Qadri Makedonka Mitreva David A Rasko James M Fleckenstein |
author_facet |
F Matthew Kuhlmann John Martin Tracy H Hazen Tim J Vickers Madeline Pashos Pablo C Okhuysen Oscar G Gómez-Duarte Elizabeth Cebelinski Dave Boxrud Felipe Del Canto Roberto Vidal Firdausi Qadri Makedonka Mitreva David A Rasko James M Fleckenstein |
author_sort |
F Matthew Kuhlmann |
title |
Conservation and global distribution of non-canonical antigens in Enterotoxigenic Escherichia coli. |
title_short |
Conservation and global distribution of non-canonical antigens in Enterotoxigenic Escherichia coli. |
title_full |
Conservation and global distribution of non-canonical antigens in Enterotoxigenic Escherichia coli. |
title_fullStr |
Conservation and global distribution of non-canonical antigens in Enterotoxigenic Escherichia coli. |
title_full_unstemmed |
Conservation and global distribution of non-canonical antigens in Enterotoxigenic Escherichia coli. |
title_sort |
conservation and global distribution of non-canonical antigens in enterotoxigenic escherichia coli. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2019 |
url |
https://doi.org/10.1371/journal.pntd.0007825 https://doaj.org/article/a808e145e78f402ea679a8910db41b1f |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 13, Iss 11, p e0007825 (2019) |
op_relation |
https://doi.org/10.1371/journal.pntd.0007825 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0007825 https://doaj.org/article/a808e145e78f402ea679a8910db41b1f |
op_doi |
https://doi.org/10.1371/journal.pntd.0007825 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
13 |
container_issue |
11 |
container_start_page |
e0007825 |
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1766339831210704896 |