PXD044230 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_06:00:59.352.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 |
Dataset History
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. |
Publication List
Keyword List
submitter keyword: MS-CETSA, thermal proteome profiling, drug discovery,TPP, CETSA, thermal profiling |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD044230
- Label: PRIDE project
- Name: Thermal proteome profiling of stationary-phase E. coli treated with semapimod