PXD065411

PXD065411 is an original dataset announced via ProteomeXchange.

Title	Arylsulfamates inhibit colonic Bacteroides growth through lipid kinases and not sulfatases
Description	Excessive degradation of the colonic mucin layer by Bacteroides within the human gut microbiota drives inflammatory bowel disease in mice. Bacterial carbohydrate sulfatases are key enzymes in gut colonization, as they are elevated in human inflammatory bowel disease and correlate with disease severity. Selective inhibitors of carbohydrate sulfatases could function as sulfatase-selective drugs, allowing precise control of sulfatase activity while preserving these otherwise beneficial bacteria. Arylsulfamates are covalent inhibitors that target a catalytic formylglycine residue of steroid sulfatases, which is also conserved in carbohydrate sulfatases. Here, using a library of aryl- and carbohydrate sulfamates, we find that they are ineffective against Bacteroides carbohydrate sulfatases yet can inhibit human gut microbiota species grown on sulfated glycans. Leveraging thermal proteome profiling, we identify a lipid kinase as the target responsible for these effects. This work highlights the imperative for developing specific inhibitors targeting carbohydrate sulfatases and unveils the adverse effect that arylsulfamates have on Bacteroides species of the human gut microbiota.
HostingRepository	PRIDE
AnnounceDate	2025-07-28
AnnouncementXML	Submission_2025-07-27_16:32:45.529.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	S.S van der Post
SpeciesList	scientific name: Bacteria; NCBI TaxID: NCBITaxon:2; scientific name: Bacteroides thetaiotaomicron (strain ATCC 29148 / DSM 2079 / NCTC 10582 / E50 / VPI-5482); NCBI TaxID: 226186;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-06-24 14:17:00	ID requested
⏵ 1	2025-07-27 16:32:46	announced

10.1073/pnas.2414331122;

Crawford CJ, Tomlinson CWE, Gunawan C, Chen Z, Byrne DP, Darby C, Conti MLG, Larson T, Luis AS, Elli S, Yates EA, Bolam DN, van der Post S, Williams SJ, Cartmell A, Arylsulfamates inhibit colonic Bacteroidota growth through a sulfatase-independent mechanism. Proc Natl Acad Sci U S A, 122(28):e2414331122(2025) [pubmed]

submitter keyword: Sulfatase,Bacteroides thetaiotaomicron, Thermal proteome profiling, Arylsulfamate

Sjoerd van der Post
contact affiliation	Department of Medical Biochemistry and Cell Biology, University of Gothenburg, Gothenburg, Sweden
contact email	sjoerd.van.der.post@medkem.gu.se
lab head
S.S van der Post
contact affiliation	Medical Chemistry
contact email	sjoerd.van.der.post@medkem.gu.se
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD065411
     1. Label: PRIDE project
     2. Name: Arylsulfamates inhibit colonic Bacteroides growth through lipid kinases and not sulfatases