Clostridium difficile toxins may augment bacterial penetration of intestinal epithelium

被引:31
作者
Feltis, BA
Kim, AS
Kinneberg, KM
Lyerly, DL
Wilkins, TD
Erlandsen, SL
Wells, CL
机构
[1] Univ Minnesota, Dept Surg, Minneapolis, MN 55455 USA
[2] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA
[3] Univ Minnesota, Dept Genet, Minneapolis, MN 55455 USA
[4] Univ Minnesota, Dept Cell Biol & Dev, Minneapolis, MN 55455 USA
[5] Virginia Polytech Inst & State Univ, Dept Biochem & Anaerob Microbiol, Blacksburg, VA 24061 USA
[6] TechLab Inc, Blacksburg, VA USA
关键词
D O I
10.1001/archsurg.134.11.1235
中图分类号
R61 [外科手术学];
学科分类号
摘要
Background: Clostridium difficile can be recovered from many high-risk hospitalized patients receiving broad-spectrum antibiotic therapy. Clostridium difficile toxins A and B have been associated with increased intestinal permeability in vitro and there is growing evidence that increased intestinal permeability may be a common mechanism whereby enteric bacteria penetrate,the intestinal epithelium. Hypothesis: Clostridium difficile-induced alterations in the intestinal barrier facilitate microbial penetration of the intestinal epithelium, which in turn facilitates the translocation of intestinal bacteria. Design: Mature Caco-2 enterocytes were pretreated with varying concentrations of toxin A or toxin B followed by 1 hour of incubation with pure cultures of either Salmonella typhimurium, Escherichia coli, or Proteus mirabilis. The effects of toxins A and B on enterocyte viability, cytoskeletal actin, and ultrastructural topography were assessed using vital dyes, fluorescein-labeled phalloidin, and scanning electron microscopy, respectively. The toxins' effects on bacterial adherence and bacterial internalization by cultured enterocytes were assessed using enzyme-linked immunosorbent assay and quantitative culture, respectively. Epithelial permeability was assessed by changes in transepithelial electrical resistance and by quantifying paracellular bacterial movement through Caco-2 enterocytes cultivated on permeable supports. Results: Neither toxin A nor toxin B had a measurable effect on the numbers of enteric bacteria internalized by Caco-2 enterocytes; however, both toxins were associated with alterations in enterocyte actin, decreased transepithelial electrical resistance, and increased bacterial adherence and paracellular transmigration. Conclusion: Clostridium difficile toxins A or B may facilitate bacterial adherence and penetration of the intestinal epithelial barrier.
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页码:1235 / 1242
页数:8
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