PXD029546

PXD029546 is an original dataset announced via ProteomeXchange.

Title	Crizotinib, Tyrosine Kinase Inhibitors, Create an Antibacterial Active against Gram-positive Bacteria by Targeting the CTP Synthetase PyrG
Description	Abstract The infection of drug resistant bacteria seriously threats to public health, which makes it more urgent to find novel antibacterial compounds. Compared with traditional development approaches, drug repurposing provides a faster and more effective strategy to find new antimicrobial agents. Here, we screened an FDA-approved small-molecule library upon S. aureus, and identified crizotinib as an antimicrobial agent. We confirmed the antibacterial activities of crizotinib in vitro and in vivo by MIC, growth curve, SEM and mice experiment. At the same time, crizotinib also showed low tendency to develop resistance. Mechanistically, quantitative proteomics, bioinformatics analyses, qRT-PCR and flow cytometry biochemical validation experience confirmed that crizotinib exerted its antibacterial effects by interfering pyrimidine metabolism and disrupting DNA synthesis eventually. Furthermore, our data from drug affinity responsive target stability, bio-layer interferometry and a series of functional assays demonstrated that crizotinib could target PyrG directly in pyrimidine metabolism pathway. Taken together, our results indicated that crizotinib could be a potential antimicrobial agent to treat Gram-positive bacterial infections in the future.
HostingRepository	PRIDE
AnnounceDate	2022-03-10
AnnouncementXML	Submission_2022-03-10_05:17:06.322.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yun-Dan Zheng
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	2021-11-03 03:59:31	ID requested
⏵ 1	2022-03-10 05:17:06	announced

Dataset with its publication pending

submitter keyword: Keywords: Crizotinib, PyrG, Gram-positive, Infection

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, Jinan University, Guangzhou 510632, China
contact email	tsunxs@jnu.edu.cn
lab head
Yun-Dan Zheng
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, Guangzhou, China.
contact email	2966736437@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/2022/03/PXD029546

PRIDE project URI

• PRIDE
  1. PXD029546
     1. Label: PRIDE project
     2. Name: Crizotinib, Tyrosine Kinase Inhibitors, Create an Antibacterial Active against Gram-positive Bacteria by Targeting the CTP Synthetase PyrG