PXD044230-1

PXD044230 is an original dataset announced via ProteomeXchange.

Title	Thermal proteome profiling of stationary-phase E. coli treated with semapimod
Description	There 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.
HostingRepository	PRIDE
AnnounceDate	2024-10-08
AnnouncementXML	Submission_2024-10-08_11:39:04.319.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD044230
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Alice Herneisen
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: 562;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; methylthiolated residue; phosphorylated residue; monohydroxylated residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-31 09:38:23	ID requested
⏵ 1	2024-10-08 11:39:04	announced
2	2024-10-22 06:00:59	announced	2024-10-22: Updated project metadata.

10.6019/PXD044230;

submitter keyword: MS-CETSA, thermal proteome profiling, drug discovery,TPP, CETSA, thermal profiling

Sebastian Lourido
contact affiliation	Associate Professor, Whitehead Institute for Biomedical Research and Massachusetts Institute for Technology
contact email	lourido@wi.mit.edu
lab head
Alice Herneisen
contact affiliation	Whitehead Institute for Biomedical Research, Cambridge, MA, USA 02142 Department of Biology, Massachusetts Insitute of Technology
contact email	alice@wi.mit.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD044230
     1. Label: PRIDE project
     2. Name: Thermal proteome profiling of stationary-phase E. coli treated with semapimod