PXD062516-1

PXD062516 is an original dataset announced via ProteomeXchange.

Title	Exploring the susceptome of methicillin-resistant Staphylococcus aureus to β-Lactams using a multi-omics approach
Description	Methicillin-resistant Staphylococcus aureus (MRSA) poses a significant challenge to public health due to its evolving resistance to antibiotics. In addressing this concern, we employed a multi-omics approach, integrating proteomics and Transposon Directed Insertion-site Sequencing (TraDIS), to comprehensively investigate adaptive response of MRSA to β-lactam antibiotics and identify key genetic determinants influencing susceptibility. Proteomic analysis revealed significant shifts in the protein spectrum under sub-inhibitory concentrations of oxacillin and cefazolin, characterized by a stringent response. This included the upregulation of amino acid metabolism and oligopeptide transport pathways, along with the downregulation of arginine biosynthesis. Concurrent TraDIS screening identified 50 genes whose inactivation conferred a fitness advantage in the presence of both β-lactams, implicating processes such as nucleotide second messenger signaling, DNA repair, and histidine transport. Validation of selected mutants (relA::Tn, mutY::Tn, nsaR::Tn, aroC::Tn, SAUSA300_0432::Tn, SAUSA300_0846::Tn, SAUSA300_0595::Tn) confirmed these findings, demonstrating improved fitness in the presence of β-lactams. Integrative analysis of proteomic and TraDIS datasets highlighted the implication of the stringent response in mediating MRSA adaptation to β-lactams. These findings establish the 'susceptome' concept, a collection of genes that maintain or potentiate MRSA's vulnerability to β-lactams, providing new targets for therapeutic intervention and strategies to counteract resistance evolution.
HostingRepository	PRIDE
AnnounceDate	2025-12-12
AnnouncementXML	Submission_2025-12-12_06:52:55.548.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Nader Abdelmalek
SpeciesList	scientific name: Staphylococcus aureus; NCBI TaxID: NEWT:1280;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2025-04-02 04:48:20	ID requested
⏵ 1	2025-12-12 06:52:56	announced

10.1016/J.IJANTIMICAG.2025.107652;

submitter keyword: Protemics,MRSA, Stringent response, β-Lactams, TraDIS

Bianca Paglietti
contact affiliation	Department of Biomedical Sciences, University of Sassari, Sassari, 07100, Italy
contact email	biancap@uniss.it
lab head
Nader Abdelmalek
contact affiliation	University of Sassari
contact email	n.abdelmalek@studenti.uniss.it
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/2025/12/PXD062516

PRIDE project URI

• PRIDE
  1. PXD062516
     1. Label: PRIDE project
     2. Name: Exploring the susceptome of methicillin-resistant Staphylococcus aureus to β-Lactams using a multi-omics approach