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PXD004680

PXD004680 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleA quantitative map of beta-lactone induced virulence regulation
DescriptionBeta-lactones have recently been introduced as the first selective ClpP inhibitors that attenuate virulence of both sensitive Staphylococcus aureus and multiresistant strains (MRSA). Although previous knockout studies showed that ClpP is essential for S. aureus alpha-toxin production a link between beta-lactone inhibition and molecular virulence mechanisms has been lacking so far. We here perform a chemical-proteomic approach to elucidate anti-virulence pathways. First, we demonstrate by gel-free activity-based protein profiling that ClpP is the predominant target of beta-lactones. Only a few off-targets were discovered, which, unlike ClpP, were not involved in the reduction of alpha-toxin expression. Second, in-depth mechanistic insight was provided by a full proteomic comparison between lactone treated and untreated S. aureus cells. Quantitative mass spectrometric analysis revealed a strong up-regulation of Rot and a corresponding down-regulation of alpha-toxin, providing the first direct connection between the lactone-dependent phenotype and a corresponding cellular mechanism. By building up a quantitative virulence regulation network, we visualize the impact of ClpP inhibition in a systems biology context. Interestingly, a lack of in vitro Rot degradation by either ClpXP or ClpCP calls for an indirect mode of action that may involve ClpX-mediated RNA signaling and feed-back circuits.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_04:35:31.380.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterMatthias Stahl
SpeciesList scientific name: Staphylococcus aureus; NCBI TaxID: 1280;
ModificationListmonohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion ETD; LTQ Orbitrap XL
Dataset History
RevisionDatetimeStatusChangeLog Entry
02016-07-29 03:51:28ID requested
12017-02-08 00:55:24announced
22017-02-14 00:37:04announcedUpdated project metadata.
32017-02-23 04:26:09announcedUpdated project metadata.
42024-10-22 04:35:38announced2024-10-22: Updated project metadata.
Publication List
Krysiak J, Stahl M, Vomacka J, Fetzer C, Lakemeyer M, Fux A, Sieber SA, -Lactone-Induced Virulence Regulation. J Proteome Res, 16(3):1180-1192(2017) [pubmed]
10.1021/acs.jproteome.6b00705;
Keyword List
curator keyword: Biomedical
submitter keyword: proteomics, chemical knockout,S. aureus ClpP, antivirulence, activity-based protein profiling
Contact List
Stephan A. Sieber
contact affiliationCenter for Integrated Protein Science Munich (CIPSM) at the Department of Chemistry, Technische Universität München, Lichtenbergstraße 4, 85747 Garching b. München
contact emailstephan.sieber@mytum.de
lab head
Matthias Stahl
contact affiliationKarolinska Institutet
contact emailmatthias.stahl@ki.se
dataset submitter
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