PXD052333

PXD052333 is an original dataset announced via ProteomeXchange.

Title	A deep learning-driven discovery of berberine derivatives as novel antibacterial against multidrug-resistant Helicobacter pylori through targeting outer membrane protein transport and assembling
Description	Helicobacter pylori (H. pylori) is currently recognized as the primary carcinogenic pathogen associated with gastric tumorigenesis, and its high prevalence and resistance make it difficult to tackle. A graph neural network-based deep learning model, employing different training sets of 13,638 molecules for pre-training and fine-tuning through rigorous iterative learning processes, was aided in predicting and exploring novel molecules against H. pylori. A positively predicted novel berberine (BBR) derivative 8 with 3,13-disubstituted alkene exhibited a potency against all tested drug-susceptible and resistant H. pylori strains with minimum inhibitory concentrations (MICs) of 0.25–0.5 μg/mL. Strikingly, pharmacokinetic studies demonstrated an ideal gastric retention of 8, with the stomach concentration significantly higher than its MIC value at 24 h post dose. Oral administration of 8 and proton pump inhibitor omeprazole (OPZ) showed a 2.2-log reduction in the gastric bacterial burden compared with the control group, which is comparable to the triple-therapy, namely OPZ + amoxicillin (AMX) + clarithromycin (CLA), and partially restored the diversity of the intestinal flora as well as the abundance of probiotics. A combination of OPZ + AMX + CLA + 8 could further decrease the bacteria load (2.8-log reduction). More importantly, the mono-therapy of 8 showed comparable eradicative efficacies compared with both triple-therapy (OPZ + AMX + CLA) and the quadruple-therapy (OPZ + AMX + CLA + bismuth citrate) groups. SecA and BamD, playing a major role in outer membrane protein (OMP) transport and assembling, were identified and verified as the direct targets of 8 by employing the chemoproteomics technique. The treatment of 8 induced the death of H. pylori caused by OMP deficiency, and the subsequent reduced adhesion to gastric epithelial cells. In summary, by targeting the relatively conserved OMPs transport and assembling system, 8 has the potential to be developed as a novel anti-H. pylori candidate, especially for the eradication of drug-resistant strains. The deep learning model established in this study might provide a reliable prediction tool for future anti-H. pylori candidate discovery.
HostingRepository	PRIDE
AnnounceDate	2024-07-03
AnnouncementXML	Submission_2024-07-02_22:38:10.387.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sissi Guo
SpeciesList	scientific name: Helicobacter pylori NCTC 11637; NCBI TaxID: 102618;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2024-05-16 22:51:48	ID requested
⏵ 1	2024-07-02 22:38:10	announced

10.1038/S41392-024-01895-0;

submitter keyword: Helicobacter pylori,LC-MSMS

Wang yanxiang
contact affiliation	Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
contact email	Sissi.Kwok@outlook.com
lab head
Sissi Guo
contact affiliation	Peking Union Medical College
contact email	Sissi.Kwok@outlook.com
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/2024/07/PXD052333

PRIDE project URI

• PRIDE
  1. PXD052333
     1. Label: PRIDE project
     2. Name: A deep learning-driven discovery of berberine derivatives as novel antibacterial against multidrug-resistant Helicobacter pylori through targeting outer membrane protein transport and assembling