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PXD044230-1

PXD044230 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleThermal proteome profiling of stationary-phase E. coli treated with semapimod
DescriptionThere is a need to discover and develop non-toxic antibiotics that are effective against metabolically dormant bacteria, which underlie chronic infections and promote antibiotic resistance. Traditional antibiotic discovery has historically favored compounds effective against actively metabolizing cells, a property that is not predictive of efficacy in metabolically inactive contexts. Here, we combine a stationary-phase screening method with deep learning-powered virtual screens and toxicity filtering to discover compounds with lethality against metabolically dormant bacteria and favorable toxicity profiles. The most potent and structurally novel compound without any obvious mechanistic liability was semapimod, an anti-inflammatory drug effective against stationary-phase E. coli and A. baumannii. Integrating microbiological assays, biochemical measurements, and single-cell microscopy, we show that semapimod selectively disrupts and permeabilizes the bacterial outer membrane by binding lipopolysaccharide. This work illustrates the value of harnessing non-traditional screening methods and deep learning models to identify non-toxic antibacterial compounds that are effective in infection-relevant contexts.
HostingRepositoryPRIDE
AnnounceDate2024-10-08
AnnouncementXMLSubmission_2024-10-08_11:39:04.319.xml
DigitalObjectIdentifierhttps://dx.doi.org/10.6019/PXD044230
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterAlice Herneisen
SpeciesList scientific name: Escherichia coli; NCBI TaxID: 562;
ModificationListTMT6plex-126 reporter+balance reagent acylated residue; methylthiolated residue; phosphorylated residue; monohydroxylated residue
InstrumentOrbitrap Exploris 480
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-07-31 09:38:23ID requested
12024-10-08 11:39:04announced
22024-10-22 06:00:59announced2024-10-22: Updated project metadata.
Publication List
10.6019/PXD044230;
Keyword List
submitter keyword: MS-CETSA, thermal proteome profiling, drug discovery,TPP, CETSA, thermal profiling
Contact List
Sebastian Lourido
contact affiliationAssociate Professor, Whitehead Institute for Biomedical Research and Massachusetts Institute for Technology
contact emaillourido@wi.mit.edu
lab head
Alice Herneisen
contact affiliationWhitehead Institute for Biomedical Research, Cambridge, MA, USA 02142 Department of Biology, Massachusetts Insitute of Technology
contact emailalice@wi.mit.edu
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
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