9
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: not found
      • Article: not found

      In Colon Epithelia, Clostridium perfringens Enterotoxin Causes Focal Leaks by Targeting Claudins Which are Apically Accessible Due to Tight Junction Derangement

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Clostridium perfringens enterotoxin (CPE) causes food poisoning and antibiotic-associated diarrhea. It uses some claudin tight junction proteins (eg, claudin-4) as receptors to form Ca2+-permeable pores in the membrane, damaging epithelial cells in small intestine and colon. We demonstrate that only a subpopulation of colonic enterocytes which are characterized by apical dislocation of claudins are CPE-susceptible. CPE-mediated damage was enhanced if paracellular barrier was impaired by Ca2+ depletion, proinflammatory cytokine tumor necrosis factor α, or dedifferentiation. Microscopy, Ca2+ monitoring, and electrophysiological data showed that CPE-mediated cytotoxicity and barrier disruption was limited by extent of CPE-binding. The latter was restricted by accessibility of non-junctional claudin molecules such as claudin-4 at apical membranes. Focal-leaks detected in HT-29/B6 colonic monolayers were verified for native tissue using colon biopsies. These mechanistic findings indicate how CPE-mediated effects may turn from self-limiting diarrhea into severe clinical manifestation such as colonic necrosis-if intestinal barrier dysfunction, eg, during inflammation facilitates claudin accessibility.

          Related collections

          Author and article information

          Journal
          The Journal of Infectious Diseases
          Oxford University Press (OUP)
          0022-1899
          1537-6613
          January 01 2018
          January 01 2018
          September 15 2017
          January 01 2018
          January 01 2018
          September 15 2017
          : 217
          : 1
          : 147-157
          Affiliations
          [1 ]Institute of Clinical Physiology, Charité—Universitätsmedizin Berlin, Germany
          [2 ]Leibniz-Forschungsinstitut für Molekulare Pharmakologie, Berlin, Germany
          [3 ]Max-Delbrück-Center für Molekulare Medizin, Berlin, Germany
          Article
          10.1093/infdis/jix485
          28968861
          07cf7a9d-fafc-4206-b8d5-053d4d4d1578
          © 2017
          History

          Comments

          Comment on this article