Directed evaluation of enterotoxigenic Escherichia coli autotransporter proteins as putative vaccine candidates.
Enterotoxigenic Escherichia coli (ETEC) is a major diarrheal pathogen in developing countries, where it accounts for millions of infections and hundreds of thousands of deaths annually. While vaccine development to prevent diarrheal illness due to ETEC is feasible, extensive effort is needed to iden...
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ftdoajarticles:oai:doaj.org/article:d8880f8bd0734ea7bea539e95ec9c182 2023-05-15T15:12:12+02:00 Directed evaluation of enterotoxigenic Escherichia coli autotransporter proteins as putative vaccine candidates. Jessica A Harris Koushik Roy Virginia Woo-Rasberry David J Hamilton Rita Kansal Firdausi Qadri James M Fleckenstein 2011-12-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0001428 https://doaj.org/article/d8880f8bd0734ea7bea539e95ec9c182 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC3232201?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0001428 https://doaj.org/article/d8880f8bd0734ea7bea539e95ec9c182 PLoS Neglected Tropical Diseases, Vol 5, Iss 12, p e1428 (2011) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2011 ftdoajarticles https://doi.org/10.1371/journal.pntd.0001428 2022-12-30T23:19:51Z Enterotoxigenic Escherichia coli (ETEC) is a major diarrheal pathogen in developing countries, where it accounts for millions of infections and hundreds of thousands of deaths annually. While vaccine development to prevent diarrheal illness due to ETEC is feasible, extensive effort is needed to identify conserved antigenic targets. Pathogenic Escherichia coli, including ETEC, use the autotransporter (AT) secretion mechanism to export virulence factors. AT proteins are comprised of a highly conserved carboxy terminal outer membrane beta barrel and a surface-exposed amino terminal passenger domain. Recent immunoproteomic studies suggesting that multiple autotransporter passenger domains are recognized during ETEC infection prompted the present studies.Available ETEC genomes were examined to identify AT coding sequences present in pathogenic isolates, but not in the commensal E. coli HS strain. Passenger domains of the corresponding autotransporters were cloned and expressed as recombinant antigens, and the immune response to these proteins was then examined using convalescent sera from patients and experimentally infected mice.Potential AT genes shared by ETEC strains, but absent in the E. coli commensal HS strain were identified. Recombinant passenger domains derived from autotransporters, including Ag43 and an AT designated pAT, were recognized by antibodies from mice following intestinal challenge with H10407, and both Ag43 and pAT were identified on the surface of ETEC by flow cytometry. Likewise, convalescent sera from patients with ETEC diarrhea recognized Ag43 and pAT, suggesting that these proteins are expressed during both experimental and naturally occurring ETEC infections and that they are immunogenic. Vaccination of mice with recombinant passenger domains from either pAT or Ag43 afforded protection against intestinal colonization with ETEC.Passenger domains of conserved autotransporter proteins could contribute to protective immune responses that develop following infection with ETEC, and these ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 5 12 e1428 |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
topic |
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 Jessica A Harris Koushik Roy Virginia Woo-Rasberry David J Hamilton Rita Kansal Firdausi Qadri James M Fleckenstein Directed evaluation of enterotoxigenic Escherichia coli autotransporter proteins as putative vaccine candidates. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Enterotoxigenic Escherichia coli (ETEC) is a major diarrheal pathogen in developing countries, where it accounts for millions of infections and hundreds of thousands of deaths annually. While vaccine development to prevent diarrheal illness due to ETEC is feasible, extensive effort is needed to identify conserved antigenic targets. Pathogenic Escherichia coli, including ETEC, use the autotransporter (AT) secretion mechanism to export virulence factors. AT proteins are comprised of a highly conserved carboxy terminal outer membrane beta barrel and a surface-exposed amino terminal passenger domain. Recent immunoproteomic studies suggesting that multiple autotransporter passenger domains are recognized during ETEC infection prompted the present studies.Available ETEC genomes were examined to identify AT coding sequences present in pathogenic isolates, but not in the commensal E. coli HS strain. Passenger domains of the corresponding autotransporters were cloned and expressed as recombinant antigens, and the immune response to these proteins was then examined using convalescent sera from patients and experimentally infected mice.Potential AT genes shared by ETEC strains, but absent in the E. coli commensal HS strain were identified. Recombinant passenger domains derived from autotransporters, including Ag43 and an AT designated pAT, were recognized by antibodies from mice following intestinal challenge with H10407, and both Ag43 and pAT were identified on the surface of ETEC by flow cytometry. Likewise, convalescent sera from patients with ETEC diarrhea recognized Ag43 and pAT, suggesting that these proteins are expressed during both experimental and naturally occurring ETEC infections and that they are immunogenic. Vaccination of mice with recombinant passenger domains from either pAT or Ag43 afforded protection against intestinal colonization with ETEC.Passenger domains of conserved autotransporter proteins could contribute to protective immune responses that develop following infection with ETEC, and these ... |
format |
Article in Journal/Newspaper |
author |
Jessica A Harris Koushik Roy Virginia Woo-Rasberry David J Hamilton Rita Kansal Firdausi Qadri James M Fleckenstein |
author_facet |
Jessica A Harris Koushik Roy Virginia Woo-Rasberry David J Hamilton Rita Kansal Firdausi Qadri James M Fleckenstein |
author_sort |
Jessica A Harris |
title |
Directed evaluation of enterotoxigenic Escherichia coli autotransporter proteins as putative vaccine candidates. |
title_short |
Directed evaluation of enterotoxigenic Escherichia coli autotransporter proteins as putative vaccine candidates. |
title_full |
Directed evaluation of enterotoxigenic Escherichia coli autotransporter proteins as putative vaccine candidates. |
title_fullStr |
Directed evaluation of enterotoxigenic Escherichia coli autotransporter proteins as putative vaccine candidates. |
title_full_unstemmed |
Directed evaluation of enterotoxigenic Escherichia coli autotransporter proteins as putative vaccine candidates. |
title_sort |
directed evaluation of enterotoxigenic escherichia coli autotransporter proteins as putative vaccine candidates. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2011 |
url |
https://doi.org/10.1371/journal.pntd.0001428 https://doaj.org/article/d8880f8bd0734ea7bea539e95ec9c182 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 5, Iss 12, p e1428 (2011) |
op_relation |
http://europepmc.org/articles/PMC3232201?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0001428 https://doaj.org/article/d8880f8bd0734ea7bea539e95ec9c182 |
op_doi |
https://doi.org/10.1371/journal.pntd.0001428 |
container_title |
PLoS Neglected Tropical Diseases |
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5 |
container_issue |
12 |
container_start_page |
e1428 |
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1766342920645902336 |