PXD007259

PXD007259 is an original dataset announced via ProteomeXchange.

Title	A Chemical Disruptor of the ClpX Chaperone Complex Attenuates Multiresistant Staphylococcus aureus Virulence
Description	The Staphylococcus aureus ClpXP protease is an important regulator of cell homeostasis and virulence. Here we utilize a high-throughput screen against the ClpXP complex and identify a specific inhibitor of the ClpX chaperone that disrupts its oligomeric state. Synthesis of 34 derivatives revealed that the molecular scaffold is restrictive for diversification with only minor changes tolerated. Subsequent analysis of the most active compound revealed strong attenuation of S. aureus toxin production which was quantified via a novel MS-based assay platform. Transcriptome and whole proteome studies further confirmed the global reduction of virulence and unraveled characteristic signatures of protein expression in compound treated cells. Although these partially matched the pattern of ClpX knockout cells, further depletion of toxins was observed leading to the intriguing perspective that additional virulence pathways may be directly or indirectly addressed by the small molecule.
HostingRepository	PRIDE
AnnounceDate	2017-09-14
AnnouncementXML	Submission_2017-09-18_07:41:06.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christian Fetzer
SpeciesList	scientific name: Staphylococcus aureus; NCBI TaxID: 1280;
ModificationList	iodoacetamide derivatized residue
Instrument	LTQ Orbitrap XL; Orbitrap Fusion; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2017-08-14 00:23:43	ID requested
1	2017-09-14 06:37:56	announced
⏵ 2	2017-09-18 07:41:07	announced	Updated publication reference for PubMed record(s): 28906057.

Fetzer C, Korotkov VS, Th, ä, nert R, Lee KM, Neuenschwander M, von Kries JP, Medina E, Sieber SA, A Chemical Disruptor of the ClpX Chaperone Complex Attenuates the Virulence of Multidrug-Resistant Staphylococcus aureus. Angew Chem Int Ed Engl, 56(49):15746-15750(2017) [pubmed]

curator keyword: Biological, Biomedical

submitter keyword: antivirulence, high-throughput screening, proteolysis, proteomics, Staphylococcus aureus

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@tum.de
lab head
Christian Fetzer
contact affiliation	Technische Universität München
contact email	christian.fetzer@tum.de
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/2017/09/PXD007259

PRIDE project URI

• PRIDE
  1. PXD007259
     1. Label: PRIDE project
     2. Name: A Chemical Disruptor of the ClpX Chaperone Complex Attenuates Multiresistant Staphylococcus aureus Virulence