PXD010179

PXD010179 is an original dataset announced via ProteomeXchange.

Title	Spatiotemporal proteomics uncovers cathepsin-dependent host cell death during bacterial infection
Description	Immune cells need to swiftly and effectively respond to invading pathogens. This response relies heavily on rapid protein synthesis and accurate cellular targeting to ensure pathogen destruction. In return, pathogens intercept this response so they can survive and proliferate. To gain insight into this dynamic interface, we combined click-chemistry with pulsed stable isotope labelling of amino acids (pSILAC-AHA) and quantified the newly synthesised host proteome during macrophage infection with the model intracellular bacterial pathogen, Salmonella enterica Typhimurium (STm). We monitored newly synthesized proteins across different compartments and during different infection stages, and used available proteomics data in response to LPS to deconvolute the STm-specific response. Within this rich resource, we detect aberrant trafficking of lysosomal proteases to the extracellular space and the nucleus, the latter of which correlates with signatures of cell death. Pharmacological cathepsin inhibition suppressed caspase-11 dependent macrophage cell death, thus demonstrating an active role for cathepsins during STm induced pyroptosis. Our study illustrates the utility of resolving the host proteome dynamics during infection to drive the discovery of novel biological mechanisms at the host-microbe interface.
HostingRepository	PRIDE
AnnounceDate	2020-01-24
AnnouncementXML	Submission_2020-06-15_02:56:43.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sophia Foehr
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2018-06-21 06:09:34	ID requested
1	2020-01-24 02:18:31	announced
⏵ 2	2020-06-15 02:56:44	announced	2020-06-15: Updated publication reference for PubMed record(s): 32514074.

Selkrig J, Li N, Hausmann A, Mangan MSJ, Zietek M, Mateus A, Bobonis J, Sueki A, Imamura H, El Debs B, Sigismondo G, Florea BI, Overkleeft HS, Kopitar-Jerala N, Turk B, Beltrao P, Savitski MM, Latz E, Hardt WD, Krijgsveld J, Typas A, Spatiotemporal proteomics uncovers cathepsin-dependent macrophage cell death during Salmonella infection. Nat Microbiol, 5(9):1119-1133(2020) [pubmed]

curator keyword: Biomedical

submitter keyword: pulse SILAC, azidohomoalanine (AHA), salmonella, infection, cathepsin

Jeroen Krijgsveld
contact affiliation	DKFZ German Cancer Research Center
contact email	j.krijgsveld@dkfz.de
lab head
Sophia Foehr
contact affiliation	DKFZ
contact email	sophia.foehr@dkfz.de
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/2020/01/PXD010179

PRIDE project URI

• PRIDE
  1. PXD010179
     1. Label: PRIDE project
     2. Name: Spatiotemporal proteomics uncovers cathepsin-dependent host cell death during bacterial infection