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Functional and structural consequences of epithelial cell invasion by Bordetella pertussis adenylate cyclase toxin
Bordetella pertussis, the causative agent of whopping cough, produces an adenylate cyclase toxin (CyaA) that plays a key role in the host colonization by targeting innate immune cells which express CD11b/CD18, the cellular receptor of CyaA. CyaA is also able to invade non-phagocytic cells, via a uni...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7213728/ https://www.ncbi.nlm.nih.gov/pubmed/32392246 http://dx.doi.org/10.1371/journal.pone.0228606 |
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author | Angely, Christelle Ladant, Daniel Planus, Emmanuelle Louis, Bruno Filoche, Marcel Chenal, Alexandre Isabey, Daniel |
author_facet | Angely, Christelle Ladant, Daniel Planus, Emmanuelle Louis, Bruno Filoche, Marcel Chenal, Alexandre Isabey, Daniel |
author_sort | Angely, Christelle |
collection | PubMed |
description | Bordetella pertussis, the causative agent of whopping cough, produces an adenylate cyclase toxin (CyaA) that plays a key role in the host colonization by targeting innate immune cells which express CD11b/CD18, the cellular receptor of CyaA. CyaA is also able to invade non-phagocytic cells, via a unique entry pathway consisting in a direct translocation of its catalytic domain across the cytoplasmic membrane of the cells. Within the cells, CyaA is activated by calmodulin to produce high levels of cyclic adenosine monophosphate (cAMP) and alter cellular physiology. In this study, we explored the effects of CyaA toxin on the cellular and molecular structure remodeling of A549 alveolar epithelial cells. Using classical imaging techniques, biochemical and functional tests, as well as advanced cell mechanics method, we quantify the structural and functional consequences of the massive increase of intracellular cyclic AMP induced by the toxin: cell shape rounding associated to adhesion weakening process, actin structure remodeling for the cortical and dense components, increase in cytoskeleton stiffness, and inhibition of migration and repair. We also show that, at low concentrations (0.5 nM), CyaA could significantly impair the migration and wound healing capacities of the intoxicated alveolar epithelial cells. As such concentrations might be reached locally during B. pertussis infection, our results suggest that the CyaA, beyond its major role in disabling innate immune cells, might also contribute to the local alteration of the epithelial barrier of the respiratory tract, a hallmark of pertussis. |
format | Online Article Text |
id | pubmed-7213728 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-72137282020-05-26 Functional and structural consequences of epithelial cell invasion by Bordetella pertussis adenylate cyclase toxin Angely, Christelle Ladant, Daniel Planus, Emmanuelle Louis, Bruno Filoche, Marcel Chenal, Alexandre Isabey, Daniel PLoS One Research Article Bordetella pertussis, the causative agent of whopping cough, produces an adenylate cyclase toxin (CyaA) that plays a key role in the host colonization by targeting innate immune cells which express CD11b/CD18, the cellular receptor of CyaA. CyaA is also able to invade non-phagocytic cells, via a unique entry pathway consisting in a direct translocation of its catalytic domain across the cytoplasmic membrane of the cells. Within the cells, CyaA is activated by calmodulin to produce high levels of cyclic adenosine monophosphate (cAMP) and alter cellular physiology. In this study, we explored the effects of CyaA toxin on the cellular and molecular structure remodeling of A549 alveolar epithelial cells. Using classical imaging techniques, biochemical and functional tests, as well as advanced cell mechanics method, we quantify the structural and functional consequences of the massive increase of intracellular cyclic AMP induced by the toxin: cell shape rounding associated to adhesion weakening process, actin structure remodeling for the cortical and dense components, increase in cytoskeleton stiffness, and inhibition of migration and repair. We also show that, at low concentrations (0.5 nM), CyaA could significantly impair the migration and wound healing capacities of the intoxicated alveolar epithelial cells. As such concentrations might be reached locally during B. pertussis infection, our results suggest that the CyaA, beyond its major role in disabling innate immune cells, might also contribute to the local alteration of the epithelial barrier of the respiratory tract, a hallmark of pertussis. Public Library of Science 2020-05-11 /pmc/articles/PMC7213728/ /pubmed/32392246 http://dx.doi.org/10.1371/journal.pone.0228606 Text en © 2020 Angely et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Angely, Christelle Ladant, Daniel Planus, Emmanuelle Louis, Bruno Filoche, Marcel Chenal, Alexandre Isabey, Daniel Functional and structural consequences of epithelial cell invasion by Bordetella pertussis adenylate cyclase toxin |
title | Functional and structural consequences of epithelial cell invasion by Bordetella pertussis adenylate cyclase toxin |
title_full | Functional and structural consequences of epithelial cell invasion by Bordetella pertussis adenylate cyclase toxin |
title_fullStr | Functional and structural consequences of epithelial cell invasion by Bordetella pertussis adenylate cyclase toxin |
title_full_unstemmed | Functional and structural consequences of epithelial cell invasion by Bordetella pertussis adenylate cyclase toxin |
title_short | Functional and structural consequences of epithelial cell invasion by Bordetella pertussis adenylate cyclase toxin |
title_sort | functional and structural consequences of epithelial cell invasion by bordetella pertussis adenylate cyclase toxin |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7213728/ https://www.ncbi.nlm.nih.gov/pubmed/32392246 http://dx.doi.org/10.1371/journal.pone.0228606 |
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