PXD067473

PXD067473 is an original dataset announced via ProteomeXchange.

Title	Dual-targeting 5-nitroimidazole ethers eradicate H. pylori by induction of stress and disabling its adaptive response
Description	Metronidazole represents a front line-drug against Helicobacter pylori. To unravel its largely unknown cellular targets, we performed activity-based protein profiling (ABPP). Surprisingly, an alkynylated ether probe (Metro-P3) exhibited a 60-fold enhanced potency. Chaperonin HpGroEL and thiol peroxidase HpTpx were identified as prominent Metro-P3 targets, the latter of which is essential for H. pylori survival under oxidative stress. Biological assays validated HpTpx inhibition as the origin of the activity boost, demonstrated by covalent modification of the catalytic cysteine and co-crystallization. Metro-P3 and refined ether analogs exhibited favorable pharmacological profiles with no cytotoxicity. The activity boost translated to an in vivo H. pylori mouse model demonstrating full eradication at 50-fold reduced dosing compared to metronidazole triple therapy. Our results highlight 5-nitroimidazole ethers as dual mode of action antibiotics which induce oxidative stress and inhibit the stress response leading to bacterial death.
HostingRepository	PRIDE
AnnounceDate	2026-04-13
AnnouncementXML	Submission_2026-04-12_16:57:05.083.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marianne Pandler
SpeciesList	scientific name: Staphylococcus schleiferi; NCBI TaxID: NEWT:1295; scientific name: Staphylococcus pseudintermedius; NCBI TaxID: NEWT:283734;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2025-08-18 08:47:11	ID requested
⏵ 1	2026-04-12 16:57:06	announced

10.1038/s41564-026-02291-w;

Fiedler MK, Pandler MSI, Gong R, Fuchs S, Rox K, Friedrich V, Pfeiffer D, Singh D, Reinhardt T, Mibus C, Huber M, Hess CR, Mej, í, as-Luque R, Gerhard M, Groll M, Sieber SA, Metronidazole and ether derivatives target Helicobacter pylori via simultaneous stress induction and inhibition. Nat Microbiol, 11(4):1049-1063(2026) [pubmed]

submitter keyword: ABPP, LC-MSMS,Bacteria

Stephan Axel Sieber
contact affiliation	TUM School of Natural Sciences, Department Biosciences, Chair of Organic Chemistry II, Center for Functional Protein Assemblies (CPA), Technical University Munich (TUM); Ernst-Otto-Fischer Str. 8, 85748 Garching, Germany
contact email	stephan.sieber@tum.de
lab head
Marianne Pandler
contact affiliation	TUM
contact email	marianne.pandler@tum.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD067473

PRIDE project URI

• PRIDE
  1. PXD067473
     1. Label: PRIDE project
     2. Name: Dual-targeting 5-nitroimidazole ethers eradicate H. pylori by induction of stress and disabling its adaptive response