MassIVE MSV000084899

Imported Reanalysis Dataset Public PXD010174

An Outer Membrane Protein-Targeting Antibiotic Against Resistant Gram-Negative Bacterial Pathogens

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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. [dataset license: CC0 1.0 Universal (CC0 1.0)]

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

Contact

Principal Investigators:
(in alphabetical order) 		Bernd Wollscheid, Institute of Molecular Systems Biology & Department of Health Sciences and Technology, ETH Zurich, Switzerland, N/A
Submitting User: ccms

Publications

Luther A, Urfer M, Zahn M, Müller 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, Desjonquères N, Brabet E, Hell S, LePoupon K, Vermeulen A, Jaisson R, Rithié 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. 2019 Dec;576(7787):452-458. Epub 2019 Oct 23.

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Number of distinct conditions across all analyses (original submission and reanalyses) associated with this dataset.

Distinct condition labels are counted across all files submitted in the "Metadata" category having a "Condition" column in this dataset.

"N/A" means no results of this type were submitted.
Number of distinct biological replicates across all analyses (original submission and reanalyses) associated with this dataset.

Distinct replicate labels are counted across all files submitted in the "Metadata" category having a "BioReplicate" or "Replicate" column in this dataset.

"N/A" means no results of this type were submitted.
Number of distinct technical replicates across all analyses (original submission and reanalyses) associated with this dataset.

The technical replicate count is defined as the maximum number of times any one distinct combination of condition and biological replicate was analyzed across all files submitted in the "Metadata" category. In the case of fractionated experiments, only the first fraction is considered.

"N/A" means no results of this type were submitted.
Originally identified proteins that were automatically remapped by MassIVE to proteins in the SwissProt human reference database.

"N/A" means no results of this type were submitted.
Number of distinct protein accessions reported across all analyses (original submission and reanalyses) associated with this dataset.

"N/A" means no results of this type were submitted.
Number of distinct unmodified peptide sequences reported across all analyses (original submission and reanalyses) associated with this dataset.

"N/A" means no results of this type were submitted.
Number of distinct peptide sequences (including modified variants or peptidoforms) reported across all analyses (original submission and reanalyses) associated with this dataset.

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Total number of peptide-spectrum matches (i.e. spectrum identifications) reported across all analyses (original submission and reanalyses) associated with this dataset.

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Number of distinct proteins quantified across all analyses (original submission and reanalyses) associated with this dataset.

Distinct protein accessions are counted across all files submitted in the "Statistical Analysis of Quantified Analytes" category having a "Protein" column in this dataset.

"N/A" means no results of this type were submitted.
Number of distinct proteins found to be differentially abundant in at least one comparison across all analyses (original submission and reanalyses) associated with this dataset.

A protein is differentially abundant if its change in abundance across conditions is found to be statistically significant with an adjusted p-value <= 0.05 and lists no issues associated with statistical tests for differential abundance.

Distinct protein accessions are counted across all files submitted in the "Statistical Analysis of Quantified Analytes" category having a "Protein" column in this dataset.

"N/A" means no results of this type were submitted.
This dataset may not contain all raw spectra data as originally deposited in PRIDE. It has been imported to MassIVE for reanalysis purposes, so its spectra data here may consist solely of processed peak lists suitable for reanalysis with most software.