PXD024771

PXD024771 is an original dataset announced via ProteomeXchange.

Title	Gefitinib results in robust host-directed immunity against Salmonella infection through proteo-metabolomic reprogramming.
Description	The rise of antibiotic-resistant strains of Salmonella has demand the development of alternative therapeutic strategies. Recent studies have shown that targeting host factors may provide an alternative approach for the treatment of intracellular pathogens. Host-directed therapy (HDT) modulates host cellular factors that are essential to support the replication of the intracellular pathogens. In the current study, we identified Gefitinib as a potential host directed therapeutic drug against Salmonella. Further, using the proteome analysis of Salmonella-infected macrophages, we identified EGFR, a host factor, promoting intracellular survival of Salmonella via mTOR-HIF-1α axis. Blocking of EGFR, mTOR or HIF-1α inhibits the intracellular survival of Salmonella within the macrophages and in mice. Global proteo-metabolomics profiling indicated the upregulation of host factors predominantly associated with ATP turn over, glycolysis, urea cycle, which ultimately promote the activation of EGFR-HIF1α signalling upon infection. Importantly, inhibition of EGFR and HIF1α restored both proteomics and metabolomics changes caused by Salmonella infection. Taken together, this study identifies Gefitinib as a host directed drug that holds potential translational values against Salmonella infection and might be useful for the treatment of other intracellular infections.
HostingRepository	PRIDE
AnnounceDate	2021-03-26
AnnouncementXML	Submission_2021-03-25_23:23:18.747.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Bhoj Kumar
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2021-03-16 06:03:42	ID requested
⏵ 1	2021-03-25 23:23:19	announced

Dataset with its publication pending

submitter keyword: Salmonella, THP-1, SWATH-MS, DIA, Proteo-Metabolomic

Amit Awasthi
contact affiliation	Translational Health Science and Technology Institute, NCR-Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon expressway, Faridabad, India.
contact email	aawasthi@thsti.res.in
lab head
Bhoj Kumar
contact affiliation	Regional Centre for Biotechnology NCR Biotech Science Cluster 3rd Milestone, Faridabad-Gurgaon Expressway P.O. Box No. 3, Faridabad - 121 001 Haryana (NCR Delhi), India
contact email	bhoj.kumar@rcb.res.in
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/2021/03/PXD024771

PRIDE project URI

• PRIDE
  1. PXD024771
     1. Label: PRIDE project
     2. Name: Gefitinib results in robust host-directed immunity against Salmonella infection through proteo-metabolomic reprogramming.