PXD010174

PXD010174 is an original dataset announced via ProteomeXchange.

Title	An Outer Membrane Protein-Targeting Antibiotic Against Resistant Gram-Negative Bacterial Pathogens
Description	There is an urgent need for novel antibiotics against carbapenem and 3rd generation cephalosporin-resistant Gram-negative pathogens, for which the last-resort antibiotics have lost most of their efficacy. We describe here a novel class of synthetic antibiotics that was inspired from natural product-derived scaffolds. The antibiotics have an unprecedented mechanism of action, which targets the main component (BamA) of the Bam folding machinery required for folding and insertion of ß-barrel proteins into the outer membrane of Gram-negative bacteria. This OMPTA (outer membrane protein-targeting antibiotic) class shows potent activity against multidrug-resistant Gram-negative ESKAPE pathogens and overcomes colistin-resistance both in vitro and in vivo. A clinical candidate has the potential to address life threatening Gram-negative infections with high unmet medical need.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:57:43.824.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Maik Müller
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: 562;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2018-06-21 01:53:50	ID requested
1	2019-10-21 22:27:20	announced
2	2020-01-02 06:32:04	announced	2020-01-02: Updated publication reference for PubMed record(s): 31645764.
⏵ 3	2024-10-22 04:57:51	announced	2024-10-22: Updated project metadata.

10.1038/s41586-019-1665-6;

Luther A, Urfer M, Zahn M, M, ü, ller M, Wang SY, Mondal M, Vitale A, Hartmann JB, Sharpe T, Monte FL, Kocherla H, Cline E, Pessi G, Rath P, Modaresi SM, Chiquet P, Stiegeler S, Verbree C, Remus T, Schmitt M, Kolopp C, Westwood MA, Desjonqu, è, res N, Brabet E, Hell S, LePoupon K, Vermeulen A, Jaisson R, Rithi, é V, Upert G, Lederer A, Zbinden P, Wach A, Moehle K, Zerbe K, Locher HH, Bernardini F, Dale GE, Eberl L, Wollscheid B, Hiller S, Robinson JA, Obrecht D, Chimeric peptidomimetic antibiotics against Gram-negative bacteria. Nature, 576(7787):452-458(2019) [pubmed]

curator keyword: Biological, Biomedical

submitter keyword: macrocyclic peptidomimetic antibiotics, novel molecular mode of action, Lpt complex, E.coli, DDA, OMPTA (outer membrane-targeting antibiotics), LC-MS/MS, Bam complex, photoaffinity labeling, Thermo Q-Exactive Plus, interaction mapping, photo crosslinking,Gram-negative ESKAPE pathogens

Bernd Wollscheid
contact affiliation	Institute of Molecular Systems Biology & Department of Health Sciences and Technology, ETH Zurich, Switzerland
contact email	bernd.wollscheid@hest.ethz.ch
lab head
Maik Müller
contact affiliation	ETH Zurich
contact email	maimuell@ethz.ch
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/2019/10/PXD010174

PRIDE project URI

• PRIDE
  1. PXD010174
     1. Label: PRIDE project
     2. Name: An Outer Membrane Protein-Targeting Antibiotic Against Resistant Gram-Negative Bacterial Pathogens