Hemagglutinin Protease HapA Associated With Vibrio cholerae Outer Membrane Vesicles (OMVs) Disrupts Tight and Adherens Junctions

ABSTRACT This study explores the virulence mechanisms of Vibrio cholerae, with a particular emphasis on HapA, a zinc metalloprotease delivered via outer membrane vesicles (OMVs). The findings reveal that OMV‐associated HapA disrupts the integrity of tight and adherens junctions in intestinal epithel...

Full description

Saved in:
Bibliographic Details
Main Authors: Palwasha Baryalai, David Irenaeus, Eric Toh, Madeleine Ramstedt, Bernt Eric Uhlin, Aftab Nadeem, Sun Nyunt Wai
Format: Article
Language:English
Published: Wiley 2025-05-01
Series:Journal of Extracellular Vesicles
Subjects:
Online Access:https://doi.org/10.1002/jev2.70092
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849717631422038016
author Palwasha Baryalai
David Irenaeus
Eric Toh
Madeleine Ramstedt
Bernt Eric Uhlin
Aftab Nadeem
Sun Nyunt Wai
author_facet Palwasha Baryalai
David Irenaeus
Eric Toh
Madeleine Ramstedt
Bernt Eric Uhlin
Aftab Nadeem
Sun Nyunt Wai
author_sort Palwasha Baryalai
collection DOAJ
description ABSTRACT This study explores the virulence mechanisms of Vibrio cholerae, with a particular emphasis on HapA, a zinc metalloprotease delivered via outer membrane vesicles (OMVs). The findings reveal that OMV‐associated HapA disrupts the integrity of tight and adherens junctions in intestinal epithelial cell models more effectively than its purified counterpart, suggesting that association with OMVs substantially potentiates the pathogenic effects of HapA. The study further details the uptake of V. cholerae OMVs by epithelial cells, as well as their targeted degradation of key junctional proteins, including claudin, ZO‐1, and β‐catenin. These results highlight the critical role of OMV‐associated HapA in compromising epithelial barrier function. Additionally, the use of spheroids and intestinal organoids in our experiments provides deeper insight into bacterial pathogenesis, offering valuable information for the development of targeted therapeutic strategies.
format Article
id doaj-art-9ea714ac3c8d4eefa1ce83beade10bbf
institution DOAJ
issn 2001-3078
language English
publishDate 2025-05-01
publisher Wiley
record_format Article
series Journal of Extracellular Vesicles
spelling doaj-art-9ea714ac3c8d4eefa1ce83beade10bbf2025-08-20T03:12:35ZengWileyJournal of Extracellular Vesicles2001-30782025-05-01145n/an/a10.1002/jev2.70092Hemagglutinin Protease HapA Associated With Vibrio cholerae Outer Membrane Vesicles (OMVs) Disrupts Tight and Adherens JunctionsPalwasha Baryalai0David Irenaeus1Eric Toh2Madeleine Ramstedt3Bernt Eric Uhlin4Aftab Nadeem5Sun Nyunt Wai6Department of Molecular Biology and Umeå Centre for Microbial Research (UCMR) Umeå University Umeå SwedenDepartment of Molecular Biology and Umeå Centre for Microbial Research (UCMR) Umeå University Umeå SwedenDepartment of Molecular Biology and Umeå Centre for Microbial Research (UCMR) Umeå University Umeå SwedenDepartment of Chemistry and Umeå Centre for Microbial Research (UCMR) Umeå University Umeå SwedenDepartment of Molecular Biology and Umeå Centre for Microbial Research (UCMR) Umeå University Umeå SwedenDepartment of Molecular Biology and Umeå Centre for Microbial Research (UCMR) Umeå University Umeå SwedenDepartment of Molecular Biology and Umeå Centre for Microbial Research (UCMR) Umeå University Umeå SwedenABSTRACT This study explores the virulence mechanisms of Vibrio cholerae, with a particular emphasis on HapA, a zinc metalloprotease delivered via outer membrane vesicles (OMVs). The findings reveal that OMV‐associated HapA disrupts the integrity of tight and adherens junctions in intestinal epithelial cell models more effectively than its purified counterpart, suggesting that association with OMVs substantially potentiates the pathogenic effects of HapA. The study further details the uptake of V. cholerae OMVs by epithelial cells, as well as their targeted degradation of key junctional proteins, including claudin, ZO‐1, and β‐catenin. These results highlight the critical role of OMV‐associated HapA in compromising epithelial barrier function. Additionally, the use of spheroids and intestinal organoids in our experiments provides deeper insight into bacterial pathogenesis, offering valuable information for the development of targeted therapeutic strategies.https://doi.org/10.1002/jev2.70092adherens junctionscholeraouter membrane vesiclesproteasetight junctionsvirulence
spellingShingle Palwasha Baryalai
David Irenaeus
Eric Toh
Madeleine Ramstedt
Bernt Eric Uhlin
Aftab Nadeem
Sun Nyunt Wai
Hemagglutinin Protease HapA Associated With Vibrio cholerae Outer Membrane Vesicles (OMVs) Disrupts Tight and Adherens Junctions
Journal of Extracellular Vesicles
adherens junctions
cholera
outer membrane vesicles
protease
tight junctions
virulence
title Hemagglutinin Protease HapA Associated With Vibrio cholerae Outer Membrane Vesicles (OMVs) Disrupts Tight and Adherens Junctions
title_full Hemagglutinin Protease HapA Associated With Vibrio cholerae Outer Membrane Vesicles (OMVs) Disrupts Tight and Adherens Junctions
title_fullStr Hemagglutinin Protease HapA Associated With Vibrio cholerae Outer Membrane Vesicles (OMVs) Disrupts Tight and Adherens Junctions
title_full_unstemmed Hemagglutinin Protease HapA Associated With Vibrio cholerae Outer Membrane Vesicles (OMVs) Disrupts Tight and Adherens Junctions
title_short Hemagglutinin Protease HapA Associated With Vibrio cholerae Outer Membrane Vesicles (OMVs) Disrupts Tight and Adherens Junctions
title_sort hemagglutinin protease hapa associated with vibrio cholerae outer membrane vesicles omvs disrupts tight and adherens junctions
topic adherens junctions
cholera
outer membrane vesicles
protease
tight junctions
virulence
url https://doi.org/10.1002/jev2.70092
work_keys_str_mv AT palwashabaryalai hemagglutininproteasehapaassociatedwithvibriocholeraeoutermembranevesiclesomvsdisruptstightandadherensjunctions
AT davidirenaeus hemagglutininproteasehapaassociatedwithvibriocholeraeoutermembranevesiclesomvsdisruptstightandadherensjunctions
AT erictoh hemagglutininproteasehapaassociatedwithvibriocholeraeoutermembranevesiclesomvsdisruptstightandadherensjunctions
AT madeleineramstedt hemagglutininproteasehapaassociatedwithvibriocholeraeoutermembranevesiclesomvsdisruptstightandadherensjunctions
AT berntericuhlin hemagglutininproteasehapaassociatedwithvibriocholeraeoutermembranevesiclesomvsdisruptstightandadherensjunctions
AT aftabnadeem hemagglutininproteasehapaassociatedwithvibriocholeraeoutermembranevesiclesomvsdisruptstightandadherensjunctions
AT sunnyuntwai hemagglutininproteasehapaassociatedwithvibriocholeraeoutermembranevesiclesomvsdisruptstightandadherensjunctions