PXD073012

PXD073012 is an original dataset announced via ProteomeXchange.

Title	Oxadiazolone derivatives block Staphylococcus aureus growth and biofilm formation by covalently binding to strategic (Ser/Cys)-based enzymes
Description	Staphylococcus aureus is a Gram-positive opportunistic pathogen and a top-priority bacterium in the fight against antimicrobial resistance. Its high propensity to mutate, develop resistance, and become more virulent, as well as its ability to form biofilms, results in difficult-to-treat infections against which new chemical classes are urgently needed. Here, we investigated the antibacterial activity of oxadiazolone-core derivatives (OX) against planktonic and biofilm-associated S. aureus. Among the tested compounds, MpPPOX exhibits a strong bactericidal effect on extracellular bacteria with similar MIC to that of Vancomycin; iBPOX mainly inhibits intracellular bacterial growth; while HPOX strongly impair biofilm formation. Such a divergence in activity prompted us to identify their potential target enzymes via activity-based protein profiling combined with mass spectrometry. Although the most active MpPPOX inhibitor targets multiple (Ser/Cys)-based enzymes, the antibiofilm HPOX compound primarily reacts with enzymes involved in biofilm formation and virulence. Among them, the FabH protein has been confirmed as a vulnerable target of MpPPOX. Overall, this study underscores the multi-target nature of the OXs covalently bind to several (Ser/Cys)-based enzymes of interest. This binding property makes them highly versatile chemotypes that could be used as broad-spectrum antimicrobial and anti-virulence agents to potentiate otherwise ineffective or poorly active drugs.
HostingRepository	PRIDE
AnnounceDate	2026-04-01
AnnouncementXML	Submission_2026-04-01_08:57:57.653.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	AUDEBERT Stephane
SpeciesList	scientific name: Staphylococcus aureus; NCBI TaxID: NEWT:1280;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2026-01-13 09:15:45	ID requested
⏵ 1	2026-04-01 08:57:58	announced

Dataset with its publication pending

submitter keyword: LC-MSMS, DIA,Gram-positive bacteria

Antibiotic resistance

Antibiofilm activity

Activity-based protein profiling

FabH

Stéphane Audebert, PhD
contact affiliation	MaP, Marseille Protéomique Centre de Recherche en Cancérologie de Marseille, CRCM Inserm UMR1068, CNRS UMR7258, Aix Marseille Université U105, Institut Paoli Calmettes 27 Boulevard Leï Roure CS30059 13273 Marseille Cedex 09 France
contact email	stephane.audebert@inserm.fr
lab head
AUDEBERT Stephane
contact affiliation	Marseille Proteomic, Centre de Recherche en Cancérologie de Marseille, Inserm UMR1068, CNRS UMR7258, Aix Marseille Université U105, Institut Paoli Calmettes, 27 Boulevard Leï Roure CS30059 13273 Marseille Cedex 09 France
contact email	stephane.audebert@inserm.fr
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD073012
     1. Label: PRIDE project
     2. Name: Oxadiazolone derivatives block Staphylococcus aureus growth and biofilm formation by covalently binding to strategic (Ser/Cys)-based enzymes