title: Microbial biotransformation of DON: molecular basis for reduced toxicity.
abstract: Bacteria are able to de-epoxidize or epimerize deoxynivalenol (DON), a mycotoxin, to deepoxy-deoxynivalenol (deepoxy-DON or DOM-1) or 3-epi-deoxynivalenol (3-epi-DON), respectively. Using different approaches, the intestinal toxicity of 3 molecules was compared and the molecular basis for the reduced toxicity investigated. In human intestinal epithelial cells, deepoxy-DON and 3-epi-DON were not cytotoxic, did not change the oxygen consumption or impair the barrier function. In intestinal explants, exposure for 4 hours to 10 μM DON induced intestinal lesions not seen in explants treated with deepoxy-DON and 3-epi-DON. A pan-genomic transcriptomic analysis was performed on intestinal explants. 747 probes, representing 323 genes, were differentially expressed, between DON-treated and control explants. By contrast, no differentially expressed genes were observed between control, deepoxy-DON and 3-epi-DON treated explants. Both DON and its biotransformation products were able to fit into the pockets of the A-site of the ribosome peptidyl transferase center. DON forms three hydrogen bonds with the A site and activates MAPKinases (mitogen-activated protein kinases). By contrast deepoxy-DON and 3-epi-DON only form two hydrogen bonds and do not activate MAPKinases. Our data demonstrate that bacterial de-epoxidation or epimerization of DON altered their interaction with the ribosome, leading to an absence of MAPKinase activation and a reduced toxicity.
authors.affiliation: Toxalim, Research Center in Food Toxicology, Université de Toulouse, INRA, UMR 1331, ENVT, INP-Purpan Toulouse, France.|Université de Toulouse, INP, UMR 1331, Toxalim, Toulouse, France.|BIOMIN Research Center Technopark 1, 3430 Tulln, Austria.
authors.forename: Alix
authors.initials: A
authors.lastname: Pierron
authors.affiliation: Toxalim, Research Center in Food Toxicology, Université de Toulouse, INRA, UMR 1331, ENVT, INP-Purpan Toulouse, France.|Université de Toulouse, INP, UMR 1331, Toxalim, Toulouse, France.
authors.forename: Sabria
authors.initials: S
authors.lastname: Mimoun
authors.affiliation: Toxalim, Research Center in Food Toxicology, Université de Toulouse, INRA, UMR 1331, ENVT, INP-Purpan Toulouse, France.|Universidade Estadual de Londrina, Lab. Patologia Animal, CP 6001, Londrina, Paraná, Brazil.
authors.forename: Leticia S
authors.initials: LS
authors.lastname: Murate
authors.affiliation: Toxalim, Research Center in Food Toxicology, Université de Toulouse, INRA, UMR 1331, ENVT, INP-Purpan Toulouse, France.|Université de Toulouse, INP, UMR 1331, Toxalim, Toulouse, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Loiseau
authors.affiliation: Toxalim, Research Center in Food Toxicology, Université de Toulouse, INRA, UMR 1331, ENVT, INP-Purpan Toulouse, France.|Université de Toulouse, INP, UMR 1331, Toxalim, Toulouse, France.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Lippi
authors.affiliation: Universidade Estadual de Londrina, Lab. Patologia Animal, CP 6001, Londrina, Paraná, Brazil.
authors.forename: Ana-Paula F L
authors.initials: AP
authors.lastname: Bracarense
authors.affiliation: BIOMIN Research Center Technopark 1, 3430 Tulln, Austria.
authors.forename: Gerd
authors.initials: G
authors.lastname: Schatzmayr
authors.affiliation: Guelph Food Research Center Agriculture &Agri-Food Canada, Guelph, Ontario N1G 5C, Canada.
authors.forename: Jian Wei
authors.initials: JW
authors.lastname: He
authors.affiliation: Guelph Food Research Center Agriculture &Agri-Food Canada, Guelph, Ontario N1G 5C, Canada.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhou
authors.affiliation: BIOMIN Research Center Technopark 1, 3430 Tulln, Austria.
authors.forename: Wulf-Dieter
authors.initials: WD
authors.lastname: Moll
authors.affiliation: Toxalim, Research Center in Food Toxicology, Université de Toulouse, INRA, UMR 1331, ENVT, INP-Purpan Toulouse, France.|Université de Toulouse, INP, UMR 1331, Toxalim, Toulouse, France.
authors.forename: Isabelle P
authors.initials: IP
authors.lastname: Oswald
mesh_terms: D000818:Animals; D001419:Bacteria / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D001711:Biotransformation; D018938:Caco-2 Cells; D004847:Epithelial Cells / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007422:Intestines / Q000737:chemistry / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics*; D010101:Oxygen Consumption / Q000235:genetics; D012270:Ribosomes / Q000187:drug effects / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013552:Swine; D059467:Transcriptome / Q000187:drug effects / Q000235:genetics; D014255:Trichothecenes / Q000737:chemistry / Q000633:toxicity*
chemical_list: D014255:Trichothecenes; C048238:deepoxy-deoxynivalenol; D020928:Mitogen-Activated Protein Kinases; C007262:deoxynivalenol