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Campylobacter jejuni Triggers Signaling through Host Cell Focal Adhesions To Inhibit Cell Motility

Campylobacter jejuni is a major foodborne pathogen that exploits the focal adhesions of intestinal cells to promote invasion and cause severe gastritis. Focal adhesions are multiprotein complexes involved in bidirectional signaling between the actin cytoskeleton and the extracellular matrix. We inve...

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Autores principales: Klappenbach, Courtney M., Negretti, Nicholas M., Aaron, Jesse, Chew, Teng-Leong, Konkel, Michael E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8406305/
https://www.ncbi.nlm.nih.gov/pubmed/34425711
http://dx.doi.org/10.1128/mBio.01494-21
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author Klappenbach, Courtney M.
Negretti, Nicholas M.
Aaron, Jesse
Chew, Teng-Leong
Konkel, Michael E.
author_facet Klappenbach, Courtney M.
Negretti, Nicholas M.
Aaron, Jesse
Chew, Teng-Leong
Konkel, Michael E.
author_sort Klappenbach, Courtney M.
collection PubMed
description Campylobacter jejuni is a major foodborne pathogen that exploits the focal adhesions of intestinal cells to promote invasion and cause severe gastritis. Focal adhesions are multiprotein complexes involved in bidirectional signaling between the actin cytoskeleton and the extracellular matrix. We investigated the dynamics of focal adhesion structure and function in C. jejuni-infected cells using a comprehensive set of approaches, including confocal microscopy of live and fixed cells, immunoblotting, and superresolution interferometric photoactivated localization microscopy (iPALM). We found that C. jejuni infection of epithelial cells results in increased focal adhesion size and altered topology. These changes resulted in a persistent modulatory effect on the host cell focal adhesion, evidenced by an increase in cell adhesion strength, a decrease in individual cell motility, and a reduction in collective cell migration. We discovered that C. jejuni infection causes an increase in phosphorylation of paxillin and an alteration of paxillin turnover at the focal adhesion, which together represent a potential mechanistic basis for altered cell motility. Finally, we observed that infection of epithelial cells with the C. jejuni wild-type strain in the presence of a protein synthesis inhibitor, a C. jejuni CadF and FlpA fibronectin-binding protein mutant, or a C. jejuni flagellar export mutant blunts paxillin phosphorylation and partially reestablishes individual host cell motility and collective cell migration. These findings provide a potential mechanism for the restricted intestinal repair observed in C. jejuni-infected animals and raise the possibility that bacteria targeting extracellular matrix components can alter cell behavior after binding and internalization by manipulating focal adhesions.
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spelling pubmed-84063052021-09-09 Campylobacter jejuni Triggers Signaling through Host Cell Focal Adhesions To Inhibit Cell Motility Klappenbach, Courtney M. Negretti, Nicholas M. Aaron, Jesse Chew, Teng-Leong Konkel, Michael E. mBio Research Article Campylobacter jejuni is a major foodborne pathogen that exploits the focal adhesions of intestinal cells to promote invasion and cause severe gastritis. Focal adhesions are multiprotein complexes involved in bidirectional signaling between the actin cytoskeleton and the extracellular matrix. We investigated the dynamics of focal adhesion structure and function in C. jejuni-infected cells using a comprehensive set of approaches, including confocal microscopy of live and fixed cells, immunoblotting, and superresolution interferometric photoactivated localization microscopy (iPALM). We found that C. jejuni infection of epithelial cells results in increased focal adhesion size and altered topology. These changes resulted in a persistent modulatory effect on the host cell focal adhesion, evidenced by an increase in cell adhesion strength, a decrease in individual cell motility, and a reduction in collective cell migration. We discovered that C. jejuni infection causes an increase in phosphorylation of paxillin and an alteration of paxillin turnover at the focal adhesion, which together represent a potential mechanistic basis for altered cell motility. Finally, we observed that infection of epithelial cells with the C. jejuni wild-type strain in the presence of a protein synthesis inhibitor, a C. jejuni CadF and FlpA fibronectin-binding protein mutant, or a C. jejuni flagellar export mutant blunts paxillin phosphorylation and partially reestablishes individual host cell motility and collective cell migration. These findings provide a potential mechanism for the restricted intestinal repair observed in C. jejuni-infected animals and raise the possibility that bacteria targeting extracellular matrix components can alter cell behavior after binding and internalization by manipulating focal adhesions. American Society for Microbiology 2021-08-24 /pmc/articles/PMC8406305/ /pubmed/34425711 http://dx.doi.org/10.1128/mBio.01494-21 Text en Copyright © 2021 Klappenbach et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Klappenbach, Courtney M.
Negretti, Nicholas M.
Aaron, Jesse
Chew, Teng-Leong
Konkel, Michael E.
Campylobacter jejuni Triggers Signaling through Host Cell Focal Adhesions To Inhibit Cell Motility
title Campylobacter jejuni Triggers Signaling through Host Cell Focal Adhesions To Inhibit Cell Motility
title_full Campylobacter jejuni Triggers Signaling through Host Cell Focal Adhesions To Inhibit Cell Motility
title_fullStr Campylobacter jejuni Triggers Signaling through Host Cell Focal Adhesions To Inhibit Cell Motility
title_full_unstemmed Campylobacter jejuni Triggers Signaling through Host Cell Focal Adhesions To Inhibit Cell Motility
title_short Campylobacter jejuni Triggers Signaling through Host Cell Focal Adhesions To Inhibit Cell Motility
title_sort campylobacter jejuni triggers signaling through host cell focal adhesions to inhibit cell motility
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8406305/
https://www.ncbi.nlm.nih.gov/pubmed/34425711
http://dx.doi.org/10.1128/mBio.01494-21
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