Clostridium difficile toxins A and B can alter epithelial permeability and promote bacterial paracellular migration through HT-29 enterocytes

Brad A. Feltis, Stephen M Wiesner, Adam S. Kim, Stanley L. Erlandsen, David L. Lyerly, Tracy D. Wilkins, Carol L Wells

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Clostridium difficile toxins A and B are the widely recognized etiologic agents of antibiotic-associated diseases ranging from diarrhea to pseudomembranous colitis. We hypothesized that C. difficile toxins may alter intestinal epithelial permeability and facilitate bacterial penetration of the intestinal epithelial barrier. Experiments were designed to clarify the effects of C. difficile toxins A and B on the flux of inert particles across HT-29 enterocyte monolayers, and to correlate these results with bacteria-enterocyte interactions. In all experiments, mature, confluent HT-29 cultures were preincubated 16 h with toxin A or B (1-100 ng/mL). To study alterations in epithelial permeability, toxin-treated enterocytes were incubated with 5 pM solutions of 10-and 40-kD inert dextran particles. Toxin A, but not toxin B, was associated with increased dextran flux through enterocyte monolayers. To study bacteria-enterocyte interactions, toxin-treated enterocytes were incubated with 108 Salmonella typhimurium, Proteus mirabilis, or Escherichia coli. Although numbers of internalized bacteria were generally unaffected, both toxins were associated with increased bacterial adherence, as well as increased bacterial transmigration through enterocyte monolayers. Bacterial transmigration was significantly greater using toxin A-compared to toxin B-treated enterocytes, consistent with the observation that dextran flux was significantly greater using toxin A-compared to toxin B-treated enterocytes. Thus intestinal colonization with toxigenic C. difficile may facilitate bacterial penetration of the intestinal epithelium by a mechanism involving increased permeability of the intestinal epithelial barrier.

Original languageEnglish (US)
Pages (from-to)629-634
Number of pages6
JournalShock
Volume14
Issue number6
DOIs
StatePublished - Jan 1 2000

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Enterocytes
Permeability
Dextrans
Clostridium difficile
Bacteria
Pseudomembranous Enterocolitis
Clostridium difficile toxB protein
Clostridium difficile tcdA protein
Proteus mirabilis
Salmonella typhimurium
Intestinal Mucosa
Diarrhea
Escherichia coli
Anti-Bacterial Agents

Keywords

  • Bacteria
  • Dextran flux
  • Epithelial barrier
  • Intestine
  • Translocation

Cite this

Clostridium difficile toxins A and B can alter epithelial permeability and promote bacterial paracellular migration through HT-29 enterocytes. / Feltis, Brad A.; Wiesner, Stephen M; Kim, Adam S.; Erlandsen, Stanley L.; Lyerly, David L.; Wilkins, Tracy D.; Wells, Carol L.

In: Shock, Vol. 14, No. 6, 01.01.2000, p. 629-634.

Research output: Contribution to journalArticle

Feltis, Brad A. ; Wiesner, Stephen M ; Kim, Adam S. ; Erlandsen, Stanley L. ; Lyerly, David L. ; Wilkins, Tracy D. ; Wells, Carol L. / Clostridium difficile toxins A and B can alter epithelial permeability and promote bacterial paracellular migration through HT-29 enterocytes. In: Shock. 2000 ; Vol. 14, No. 6. pp. 629-634.
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