RT Journal
A1 Feltis B, Kim AS, Kinneberg KM, et al
T1 CLostridium difficile toxins may augment bacterial penetration of intestinal epithelium
JF Archives of Surgery
JO Archives of Surgery
YR 1999
FD November 1
VO 134
IS 11
SP 1235
OP 1242
DO 10.1001/archsurg.134.11.1235
UL http://dx.doi.org/10.1001/archsurg.134.11.1235
AB 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.