PXD041266

PXD041266 is an original dataset announced via ProteomeXchange.

Title	Repurposing cinacalcet suppresses multi-drug resistant Staphylococcus aureus by disruption of cell membrane and inhibits biofilm by targeting IcaR
Description	Multi-drug resistant Staphylococcus aureus (S. aureus) infections continously threaten public health. The rapid escalation in morbidity and mortality rates associated with methicillin-resistant S. aureus (MRSA) infections necessitates the urgent development of novel antimicrobial agents. Our study reveals that the FDA-approved drug cinacalcet (CNA) effectively functions as an antibacterial and anti-biofilm agent against S. aureus without detectable resistance. It evidently improved survival rate of mice infected with clinical multi-resistant S. aureus in a pneumonia model. Subsequent proteomic and biochemical experiments suggest that the primary antibacterial mechanism involves membrane structure disruption, ATP content reduction, and reactive oxygen species (ROS) production. Concurrently, LiP-SMap combined with biochemical validation indicates that CNA inhibits biofilm formation by targeting IcaR, a negative regulator of icaADBC, thereby enhancing its binding capacity to the ica operator DNA and subsequently suppressing extracellular polysaccharide formation. Importantly, compared to vancomycin, CNA demonstrates stronger biofilm bacterial clearance in a mouse thigh infection model. Collectively, our findings propose that CNA can be repurposed as a potential therapeutic agent for treating multidrug-resistant S. aureus infections and their associated biofilms.
HostingRepository	PRIDE
AnnounceDate	2024-02-07
AnnouncementXML	Submission_2024-02-06_18:37:43.356.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Zuye Fang
SpeciesList	scientific name: Staphylococcus aureus; NCBI TaxID: 1280;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-04-01 09:56:13	ID requested
⏵ 1	2024-02-06 18:37:43	announced

Dataset with its publication pending

submitter keyword: Mutidrug-resistance

S. aureus

Cinacalcet

IcaR

Membrane

Xuesong Sun
contact affiliation	MOE Key Laboratory of Tumor Molecular Biology and Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, China
contact email	tsunxs@jnu.edu.cn
lab head
Zuye Fang
contact affiliation	MOE Key Laboratory of Tumor Molecular Biology and Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, Jinan University
contact email	2287495655@qq.com
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/2024/02/PXD041266

PRIDE project URI

• PRIDE
  1. PXD041266
     1. Label: PRIDE project
     2. Name: Repurposing cinacalcet suppresses multi-drug resistant Staphylococcus aureus by disruption of cell membrane and inhibits biofilm by targeting IcaR