PXD025887

PXD025887 is an original dataset announced via ProteomeXchange.

Title	Specific Gut Microbial Enzymes Drive Colitis Promotion by Triclosan
Description	Triclosan (TCS), an antimicrobial agent in thousands of consumer products, is a risk factor for colitis and colitis-associated colorectal cancer. While the intestinal toxicities of TCS require the presence of gut microbiota, the molecular mechanisms involved have not been defined. Here we show that intestinal commensal microbes mediate metabolic activation of TCS in the colon and drive its gut toxicology. Using a range of in vitro, ex vivo, and in vivo approaches, we identify specific microbial β-glucuronidase (GUS) enzymes involved and pinpoint molecular motifs required to metabolically activate TCS in the gut. Finally, we show that targeted inhibition of bacterial GUS enzymes abolishes the colitis-promoting effects of TCS, supporting the essential roles of specific microbial proteins in TCS toxicity. Our results define a mechanism by which intestinal microbes cause the gut toxicity of environmental chemicals and suggest a therapeutic approach to alleviate colitis and associated diseases.
HostingRepository	PRIDE
AnnounceDate	2021-11-04
AnnouncementXML	Submission_2022-01-24_02:17:16.551.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Morgan Walker
SpeciesList	scientific name: human gut metagenome; NCBI TaxID: 408170;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-05-07 09:46:39	ID requested
1	2021-11-04 03:03:51	announced
⏵ 2	2022-01-24 02:17:17	announced	2022-01-24: Updated publication reference for PubMed record(s): 35013263.

Zhang J, Walker ME, Sanidad KZ, Zhang H, Liang Y, Zhao E, Chacon-Vargas K, Yeliseyev V, Parsonnet J, Haggerty TD, Wang G, Simpson JB, Jariwala PB, Beaty VV, Yang J, Yang H, Panigrahy A, Minter LM, Kim D, Gibbons JG, Liu L, Li Z, Xiao H, Borlandelli V, Overkleeft HS, Cloer EW, Major MB, Goldfarb D, Cai Z, Redinbo MR, Zhang G, Microbial enzymes induce colitis by reactivating triclosan in the mouse gastrointestinal tract. Nat Commun, 13(1):136(2022) [pubmed]

submitter keyword: Gut Microbiome, Triclosan, LC-MS/MS

Matthew R. Redinbo
contact affiliation	Department of Chemistry Center for Gastrointestinal Biology and Disease Integrated Program for Biological and Genome Sciences University of North Carolina at Chapel Hill
contact email	redinbo@unc.edu
lab head
Morgan Walker
contact affiliation	UNC-Chapel Hill
contact email	gibbsm@live.unc.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD025887
     1. Label: PRIDE project
     2. Name: Specific Gut Microbial Enzymes Drive Colitis Promotion by Triclosan