RESUMEN
Antibiotic-treated mice orally inoculated with one of three Candida albicans strains (including two mutant strains) or indigenous Candida pelliculosa showed levels of candidal gastrointestinal colonization that were strain specific. However, regardless of strain, the numbers of viable candida were intermediate to high in the stomach, were consistently lowest in the upper small intestine, and increased progressively down the intestinal tract.
Asunto(s)
Candidiasis/microbiología , Sistema Digestivo/microbiología , Mutación , Animales , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Bacitracina/administración & dosificación , Bacitracina/uso terapéutico , Candida albicans/enzimología , Candida albicans/genética , Candida albicans/fisiología , Candidiasis/patología , Modelos Animales de Enfermedad , Femenino , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Gentamicinas/administración & dosificación , Gentamicinas/uso terapéutico , Células HeLa , Humanos , Ratones , Orotidina-5'-Fosfato Descarboxilasa/genética , Orotidina-5'-Fosfato Descarboxilasa/metabolismo , Estreptomicina/administración & dosificación , Estreptomicina/uso terapéuticoRESUMEN
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 10(8) 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.
