<named-content content-type="genus-species">Campylobacter jejuni</named-content> Triggers Signaling through Host Cell Focal Adhesions To Inhibit Cell Motility

ABSTRACT 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...

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Autores principales:	Courtney M. Klappenbach, Nicholas M. Negretti, Jesse Aaron, Teng-Leong Chew, Michael E. Konkel
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2021
Materias:	pathogenesis focal adhesion modulation focal adhesion turnover cell migration iPALM bacterium-host cell interactions Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/c10026f112d74aa387165bff97ec5d3b
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spelling	oai:doaj.org-article:c10026f112d74aa387165bff97ec5d3b2021-11-10T18:37:51Z<named-content content-type="genus-species">Campylobacter jejuni</named-content> Triggers Signaling through Host Cell Focal Adhesions To Inhibit Cell Motility10.1128/mBio.01494-212150-7511https://doaj.org/article/c10026f112d74aa387165bff97ec5d3b2021-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01494-21https://doaj.org/toc/2150-7511ABSTRACT 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. IMPORTANCE Campylobacter jejuni is a major foodborne pathogen that causes severe gastritis. We investigated the dynamics of focal adhesion structure and function in C. jejuni-infected epithelial cells. Focal adhesions act as signaling complexes that connect the extracellular matrix to the intracellular cytoskeleton. The key findings of this study show that C. jejuni changes the structure (size and position), composition, and function of cellular focal adhesions using a combination of virulence factors. Mechanistically, we found that the changes in focal adhesion dynamics are dependent upon the activation of host cell signaling pathways, which affect the assembly and disassembly of cellular proteins from the focal adhesion. To summarize, we have identified a new cellular phenotype in C. jejuni-infected cells that may be responsible for the restricted intestinal repair observed in C. jejuni-infected animals.Courtney M. KlappenbachNicholas M. NegrettiJesse AaronTeng-Leong ChewMichael E. KonkelAmerican Society for Microbiologyarticlepathogenesisfocal adhesion modulationfocal adhesion turnovercell migrationiPALMbacterium-host cell interactionsMicrobiologyQR1-502ENmBio, Vol 12, Iss 4 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	pathogenesis focal adhesion modulation focal adhesion turnover cell migration iPALM bacterium-host cell interactions Microbiology QR1-502
spellingShingle	pathogenesis focal adhesion modulation focal adhesion turnover cell migration iPALM bacterium-host cell interactions Microbiology QR1-502 Courtney M. Klappenbach Nicholas M. Negretti Jesse Aaron Teng-Leong Chew Michael E. Konkel <named-content content-type="genus-species">Campylobacter jejuni</named-content> Triggers Signaling through Host Cell Focal Adhesions To Inhibit Cell Motility
description	ABSTRACT 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. IMPORTANCE Campylobacter jejuni is a major foodborne pathogen that causes severe gastritis. We investigated the dynamics of focal adhesion structure and function in C. jejuni-infected epithelial cells. Focal adhesions act as signaling complexes that connect the extracellular matrix to the intracellular cytoskeleton. The key findings of this study show that C. jejuni changes the structure (size and position), composition, and function of cellular focal adhesions using a combination of virulence factors. Mechanistically, we found that the changes in focal adhesion dynamics are dependent upon the activation of host cell signaling pathways, which affect the assembly and disassembly of cellular proteins from the focal adhesion. To summarize, we have identified a new cellular phenotype in C. jejuni-infected cells that may be responsible for the restricted intestinal repair observed in C. jejuni-infected animals.
format	article
author	Courtney M. Klappenbach Nicholas M. Negretti Jesse Aaron Teng-Leong Chew Michael E. Konkel
author_facet	Courtney M. Klappenbach Nicholas M. Negretti Jesse Aaron Teng-Leong Chew Michael E. Konkel
author_sort	Courtney M. Klappenbach
title	<named-content content-type="genus-species">Campylobacter jejuni</named-content> Triggers Signaling through Host Cell Focal Adhesions To Inhibit Cell Motility
title_short	<named-content content-type="genus-species">Campylobacter jejuni</named-content> Triggers Signaling through Host Cell Focal Adhesions To Inhibit Cell Motility
title_full	<named-content content-type="genus-species">Campylobacter jejuni</named-content> Triggers Signaling through Host Cell Focal Adhesions To Inhibit Cell Motility
title_fullStr	<named-content content-type="genus-species">Campylobacter jejuni</named-content> Triggers Signaling through Host Cell Focal Adhesions To Inhibit Cell Motility
title_full_unstemmed	<named-content content-type="genus-species">Campylobacter jejuni</named-content> Triggers Signaling through Host Cell Focal Adhesions To Inhibit Cell Motility
title_sort	<named-content content-type="genus-species">campylobacter jejuni</named-content> triggers signaling through host cell focal adhesions to inhibit cell motility
publisher	American Society for Microbiology
publishDate	2021
url	https://doaj.org/article/c10026f112d74aa387165bff97ec5d3b
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<named-content content-type="genus-species">Campylobacter jejuni</named-content> Triggers Signaling through Host Cell Focal Adhesions To Inhibit Cell Motility

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