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...
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| Format: | Article |
| Language: | English |
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Wiley
2025-05-01
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| Series: | Journal of Extracellular Vesicles |
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| Online Access: | https://doi.org/10.1002/jev2.70092 |
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| 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 |
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