title: Salmonella infection inhibits intestinal biotin transport: cellular and molecular mechanisms.
abstract: Infection with the nontyphoidal Salmonella is a common cause of food-borne disease that leads to acute gastroenteritis/diarrhea. Severe/prolonged cases of Salmonella infection could also impact host nutritional status, but little is known about its effect on intestinal absorption of vitamins, including biotin. We examined the effect of Salmonella enterica serovar Typhimurium (S. typhimurium) infection on intestinal biotin uptake using in vivo (streptomycin-pretreated mice) and in vitro [mouse (YAMC) and human (NCM460) colonic epithelial cells, and human intestinal epithelial Caco-2 cells] models. The results showed that infecting mice with wild-type S. typhimurium, but not with its nonpathogenic isogenic invA spiB mutant, leads to a significant inhibition in jejunal/colonic biotin uptake and in level of expression of the biotin transporter, sodium-dependent multivitamin transporter. In contrast, infecting YAMC, NCM460, and Caco-2 cells with S. typhimurium did not affect biotin uptake. These findings suggest that the effect of S. typhimurium infection is indirect and is likely mediated by proinflammatory cytokines, the levels of which were markedly induced in the intestine of S. typhimurium-infected mice. Consistent with this hypothesis, exposure of NCM460 cells to the proinflammatory cytokines TNF-α and IFN-γ led to a significant inhibition of biotin uptake, sodium-dependent multivitamin transporter expression, and activity of the SLC5A6 promoter. The latter effects appear to be mediated, at least in part, via the NF-κB signaling pathway. These results demonstrate that S. typhimurium infection inhibits intestinal biotin uptake, and that the inhibition is mediated via the action of proinflammatory cytokines.
authors.affiliation: Departments of Medicine and Physiology/Biophysics, University of California, Irvine, California; Department of Veterans Affairs Medical Center, Long Beach, California;
authors.forename: Abhisek
authors.initials: A
authors.lastname: Ghosal
authors.affiliation: Department of Microbiology and Molecular Genetics, University of California, Irvine, California; and Institute for Immunology, University of California, Irvine, California.
authors.forename: Stefan
authors.initials: S
authors.lastname: Jellbauer
authors.affiliation: Departments of Medicine and Physiology/Biophysics, University of California, Irvine, California; Department of Veterans Affairs Medical Center, Long Beach, California;
authors.forename: Rubina
authors.initials: R
authors.lastname: Kapadia
authors.affiliation: Department of Microbiology and Molecular Genetics, University of California, Irvine, California; and Institute for Immunology, University of California, Irvine, California.
authors.forename: Manuela
authors.initials: M
authors.lastname: Raffatellu
authors.affiliation: Departments of Medicine and Physiology/Biophysics, University of California, Irvine, California; Department of Veterans Affairs Medical Center, Long Beach, California; hmsaid@uci.edu.
authors.forename: Hamid M
authors.initials: HM
authors.lastname: Said
mesh_terms: D000818:Animals; D001692:Biological Transport; D001710:Biotin / Q000378:metabolism*; D018938:Caco-2 Cells; D004195:Disease Models, Animal; D054884:Host-Pathogen Interactions; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000276:immunology / Q000382:microbiology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012481:Salmonella Infections, Animal / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D012486:Salmonella typhimurium / Q000276:immunology / Q000472:pathogenicity*; D015398:Signal Transduction; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018836:Inflammation Mediators; D016328:NF-kappa B; D027981:Symporters; D014409:Tumor Necrosis Factor-alpha; C119981:biotin transporter; D001710:Biotin; D007371:Interferon-gamma
keywords: Salmonella infection; biotin; colon; intestine; transport