PXD004680

PXD004680 is an original dataset announced via ProteomeXchange.

Title	A quantitative map of beta-lactone induced virulence regulation
Description	Beta-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.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:35:31.380.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Matthias Stahl
SpeciesList	scientific name: Staphylococcus aureus; NCBI TaxID: 1280;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion ETD; LTQ Orbitrap XL

Revision	Datetime	Status	ChangeLog Entry
0	2016-07-29 03:51:28	ID requested
1	2017-02-08 00:55:24	announced
2	2017-02-14 00:37:04	announced	Updated project metadata.
3	2017-02-23 04:26:09	announced	Updated project metadata.
⏵ 4	2024-10-22 04:35:38	announced	2024-10-22: Updated project metadata.

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;

curator keyword: Biomedical

submitter keyword: proteomics, chemical knockout,S. aureus ClpP, antivirulence, activity-based protein profiling

Stephan A. Sieber
contact affiliation	Center for Integrated Protein Science Munich (CIPSM) at the Department of Chemistry, Technische Universität München, Lichtenbergstraße 4, 85747 Garching b. München
contact email	stephan.sieber@mytum.de
lab head
Matthias Stahl
contact affiliation	Karolinska Institutet
contact email	matthias.stahl@ki.se
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/02/PXD004680

PRIDE project URI

• PRIDE
  1. PXD004680
     1. Label: PRIDE project
     2. Name: A quantitative map of beta-lactone induced virulence regulation