The role of CFA/I in adherence and toxin delivery by ETEC expressing multiple colonization factors in the human enteroid model.
Enterotoxigenic Escherichia coli (ETEC) is a primary causative agent of diarrhea in travelers and young children in low-to-middle-income countries (LMICs). ETEC adhere to intestinal epithelia via colonization factors (CFs) and secrete heat-stable toxin (ST) and/or heat-labile toxin (LT), causing dys...
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ftdoajarticles:oai:doaj.org/article:2f9f6bf30456494ab1235264ef93d63e 2023-06-06T11:51:42+02:00 The role of CFA/I in adherence and toxin delivery by ETEC expressing multiple colonization factors in the human enteroid model. Emily M Smith Christen L Grassel Antonia Papadimas Jennifer Foulke-Abel Eileen M Barry 2022-07-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0010638 https://doaj.org/article/2f9f6bf30456494ab1235264ef93d63e EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0010638 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0010638 https://doaj.org/article/2f9f6bf30456494ab1235264ef93d63e PLoS Neglected Tropical Diseases, Vol 16, Iss 7, p e0010638 (2022) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2022 ftdoajarticles https://doi.org/10.1371/journal.pntd.0010638 2023-04-16T00:34:13Z Enterotoxigenic Escherichia coli (ETEC) is a primary causative agent of diarrhea in travelers and young children in low-to-middle-income countries (LMICs). ETEC adhere to intestinal epithelia via colonization factors (CFs) and secrete heat-stable toxin (ST) and/or heat-labile toxin (LT), causing dysregulated cellular ion transport and water secretion. ETEC isolates often harbor genes encoding more than one CF that are targets as vaccine antigens. CFA/I is a major CF that is associated with ETEC that causes moderate-to-severe diarrhea and plays an important role in pathogenesis. The Global Enteric Multicenter Study finding that 78% of CFA/I-expressing ETEC also encode the minor CF CS21 prompted investigation of the combined role of these two CFs. Western blots and electron microscopy demonstrated growth media-dependent and strain-dependent differences in CFA/I and CS21 expression. The critical role of CFA/I in adherence by ETEC strains expressing CFA/I and CS21 was demonstrated using the human enteroid model and a series of CFA/I- and CS21-specific mutants. Furthermore, only anti-CFA/I antibodies inhibited adherence by global ETEC isolates expressing CFA/I and CS21. Delivery of ST and resulting cGMP secretion was measured in supernatants from infected enteroid monolayers, and strain-specific ST delivery and time-dependent cGMP production was observed. Interestingly, cGMP levels were similar across wildtype and CF-deficient strains, reflecting a limitation of this static aerobic infection model. Despite adherence by ETEC and delivery of ST, the enteroid monolayer integrity was not disrupted, as shown by the lack of decrease in transepithelial electrical resistance and the lack of IL-8 cytokines produced during infection. Taken together, these data demonstrate that targeting CFA/I in global clinical CFA/I-CS21 strains is sufficient for adherence inhibition, supporting a vaccine strategy that focuses on blocking major CFs. In addition, the human enteroid model has significant utility for the study of ETEC ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 16 7 e0010638 |
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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 Emily M Smith Christen L Grassel Antonia Papadimas Jennifer Foulke-Abel Eileen M Barry The role of CFA/I in adherence and toxin delivery by ETEC expressing multiple colonization factors in the human enteroid model. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Enterotoxigenic Escherichia coli (ETEC) is a primary causative agent of diarrhea in travelers and young children in low-to-middle-income countries (LMICs). ETEC adhere to intestinal epithelia via colonization factors (CFs) and secrete heat-stable toxin (ST) and/or heat-labile toxin (LT), causing dysregulated cellular ion transport and water secretion. ETEC isolates often harbor genes encoding more than one CF that are targets as vaccine antigens. CFA/I is a major CF that is associated with ETEC that causes moderate-to-severe diarrhea and plays an important role in pathogenesis. The Global Enteric Multicenter Study finding that 78% of CFA/I-expressing ETEC also encode the minor CF CS21 prompted investigation of the combined role of these two CFs. Western blots and electron microscopy demonstrated growth media-dependent and strain-dependent differences in CFA/I and CS21 expression. The critical role of CFA/I in adherence by ETEC strains expressing CFA/I and CS21 was demonstrated using the human enteroid model and a series of CFA/I- and CS21-specific mutants. Furthermore, only anti-CFA/I antibodies inhibited adherence by global ETEC isolates expressing CFA/I and CS21. Delivery of ST and resulting cGMP secretion was measured in supernatants from infected enteroid monolayers, and strain-specific ST delivery and time-dependent cGMP production was observed. Interestingly, cGMP levels were similar across wildtype and CF-deficient strains, reflecting a limitation of this static aerobic infection model. Despite adherence by ETEC and delivery of ST, the enteroid monolayer integrity was not disrupted, as shown by the lack of decrease in transepithelial electrical resistance and the lack of IL-8 cytokines produced during infection. Taken together, these data demonstrate that targeting CFA/I in global clinical CFA/I-CS21 strains is sufficient for adherence inhibition, supporting a vaccine strategy that focuses on blocking major CFs. In addition, the human enteroid model has significant utility for the study of ETEC ... |
format |
Article in Journal/Newspaper |
author |
Emily M Smith Christen L Grassel Antonia Papadimas Jennifer Foulke-Abel Eileen M Barry |
author_facet |
Emily M Smith Christen L Grassel Antonia Papadimas Jennifer Foulke-Abel Eileen M Barry |
author_sort |
Emily M Smith |
title |
The role of CFA/I in adherence and toxin delivery by ETEC expressing multiple colonization factors in the human enteroid model. |
title_short |
The role of CFA/I in adherence and toxin delivery by ETEC expressing multiple colonization factors in the human enteroid model. |
title_full |
The role of CFA/I in adherence and toxin delivery by ETEC expressing multiple colonization factors in the human enteroid model. |
title_fullStr |
The role of CFA/I in adherence and toxin delivery by ETEC expressing multiple colonization factors in the human enteroid model. |
title_full_unstemmed |
The role of CFA/I in adherence and toxin delivery by ETEC expressing multiple colonization factors in the human enteroid model. |
title_sort |
role of cfa/i in adherence and toxin delivery by etec expressing multiple colonization factors in the human enteroid model. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2022 |
url |
https://doi.org/10.1371/journal.pntd.0010638 https://doaj.org/article/2f9f6bf30456494ab1235264ef93d63e |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 16, Iss 7, p e0010638 (2022) |
op_relation |
https://doi.org/10.1371/journal.pntd.0010638 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0010638 https://doaj.org/article/2f9f6bf30456494ab1235264ef93d63e |
op_doi |
https://doi.org/10.1371/journal.pntd.0010638 |
container_title |
PLOS Neglected Tropical Diseases |
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16 |
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7 |
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e0010638 |
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