Inhibition of Salmonella typhimurium enteropathogenicity by piperidine, a metabolite of the polyamine cadaverine.
Piperidine is a 1-ring heterocyclic compound formed from the polyamine cadaverine in the human intestine. Because heterocyclic compounds are routinely used in the promotion of antimicrobial treatment strategies, it was considered whether piperidine could be used against infection with enteric pathogens. This study demonstrates that piperidine treatment prevented the invasion of Salmonella typhimurium into model intestinal epithelium by nearly 95%. In vivo studies also revealed that it increased mouse survival and reduced S. typhimurium translocation into and colonization of various organs and tissues. Initial evaluations demonstrated that piperidine reduced the S. typhimurium-induced polymorphonuclear leukocyte transepithelial migration response in vitro by inhibiting activation of protein kinase C. Piperidine did not affect the ability of S. typhimurium to elicit interleukin-8 secretion by epithelial cells or to activate extracellular-regulated kinase signal transduction pathways. These results show that piperidine does not exhibit paninhibitory activity and suggest that piperidine may be useful in down-regulating active inflammation at mucosal surfaces.
D000818:Animals; D002103:Cadaverine / Q000378:metabolism*; D002464:Cell Migration Inhibition; D016764:Cell Polarity; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils; D010766:Phosphorylation; D010880:Piperidines / Q000378:metabolism* / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000254:growth & development / Q000472:pathogenicity* / Q000502:physiology
D016209:Interleukin-8; D010880:Piperidines; C032727:piperidine; D011493:Protein Kinase C; D002103:Cadaverine