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Cited by 195Vibrio bacteria research studiesBarrier Structure and Function StudiesEscherichia coli research studies

Distinct effects of Vibrio cholerae haemagglutinin/protease on the structure and localization of the tight junction-associated proteins occludin and ZO-1

Wu, Zhengyang, Nybom, Pia, Magnusson, Karl-Eric·2000·Cellular Microbiology
DOI 10.1046/j.1462-5822.2000.00025.x
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Abstract

Vibrio cholerae produces a little-studied cytotoxin, haemagglutinin/protease (HA/P), in addition to several better-characterized enterotoxins, i.e. cholera toxin (CT), zonula occludens toxin (ZOT) and accessory cholera enterotoxin (Ace). We have found recently that HA/P perturbs the barrier function of Mardin-Darby canine kidney epithelial cell line I (MDCK-I) by affecting the intercellular tight junctions (TJs) and the F-actin cytoskeleton. In the present study we have assessed more specifically how TJs are affected by HA/P by investigating the cellular localization and biochemical integrity of two well-characterized TJ-associated proteins, occludin and ZO-1. Western blot analysis showed that occludin bands of 66-85 kDa were digested by HA/P to two predominant bands of around 50 kDa and 35 kDa, and that this degradation was greatly attenuated when the specific bacterial metalloproteinase inhibitor Zincov was co-administered. Trypsin, on the other hand, did not degrade occludin when it was applied in the same way, suggesting that the degradation of occludin by HA/P is an early and specific event. The other TJ-associated protein ZO-1 was not degraded by HA/P in parallel experiments, suggesting the selectivity of HA/P-associated protein degradation. Moreover, immunofluorescence labelling and confocal microscopy showed that ZO-1, but not occludin, around cell-cell boundaries was rearranged by HA/P treatment. Since ZO-1 is located on the inside of the plasma membrane and is directly associated with occludin, the results indicate that breakdown of occludin may send signals to ZO-1 that affect its organization and the structure of the F-actin cytoskeleton. Our finding that the zinc-containing metalloprotease of V. cholerae specifically degraded occludin suggests that specific degradation of important host proteins by bacterial zinc-containing metalloproteases may be an important mechanism in microbial pathogenesis.

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  • Vibriolysin presents a broad range of potentially pathogenic activities including degradation of the mucus barrier or disruption of epithelial tight junctions.

    “vibriolysin presents a broad range of potentially pathogenic activities including degradation of the mucus barrier or disruption of epithelial tight junctions.10,83”

    From The emerging roles of bacterial proteases in intestinal diseases (2023) · cites this paper as [83]

  • The extracellular Zn-dependent metalloprotease hemagglutinin (vibriolysin) has been implicated in the pathogenicity of Vibrio cholerae.

    “The extracellular Zn-dependent metalloprotease hemagglutinin (HA) also called vibriolysin, has been implicated in the pathogenicity of Vibrio cholerae.”

    From The emerging roles of bacterial proteases in intestinal diseases (2023) · cites this paper as [83]

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Authors
Wu, Z., Nybom, P., & Magnusson, K.-E.
Affiliations
Linköping University (SE)
ORCID
Venue
Cellular Microbiology
Publisher
Hindawi Limited
Published
2000-02
Volume
2
Issue
1
Pages
11-17
ISSN
  • 1462-5814 (ISSN-L)
  • 1462-5822
DOI
10.1046/j.1462-5822.2000.00025.x
OpenAlex
W2150450373
Cited by
195
References
36
Citations by year
2026: 2 · 2025: 6 · 2024: 6 · 2023: 6 · 2022: 6 · 2021: 6 · 2020: 5 · 2019: 7 · 2018: 6 · 2017: 7 · 2016: 8 · 2015: 8 · 2014: 14 · 2013: 6 · 2012: 12
FWCI
4.34
Type
journal article
Language
en
Open access
closed
Licence
doi.wiley.com/10.1002/tdm_license_1.1 (tdm, 5691 d)
Locations
  • Cellular Microbiology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Vetenskapsrådet
  • Stiftelsen Professor Nanna Svartz Fond
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Vibrio bacteria research studies
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Escherichia coli research studies
Keywords
Vibrio cholerae, occludin, ZO-1, tight junctions, protein degradation, epithelial barrier function, F-actin cytoskeleton, bacterial pathogenesis
MeSH terms
Animals, Cell Line, Dogs, Epithelial Cells, Gelatin, Membrane Proteins, Metalloendopeptidases, Phosphoproteins, Trypsin, Blotting, Western, Microscopy, Confocal, Tight Junctions, Occludin, Zonula Occludens-1 Protein

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