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PXD010179

PXD010179 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleSpatiotemporal proteomics uncovers cathepsin-dependent host cell death during bacterial infection
DescriptionImmune 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.
HostingRepositoryPRIDE
AnnounceDate2020-01-24
AnnouncementXMLSubmission_2020-06-15_02:56:43.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterSophia Foehr
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListiodoacetamide derivatized residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02018-06-21 06:09:34ID requested
12020-01-24 02:18:31announced
22020-06-15 02:56:44announced2020-06-15: Updated publication reference for PubMed record(s): 32514074.
Publication List
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]
Keyword List
curator keyword: Biomedical
submitter keyword: pulse SILAC, azidohomoalanine (AHA), salmonella, infection, cathepsin
Contact List
Jeroen Krijgsveld
contact affiliationDKFZ German Cancer Research Center
contact emailj.krijgsveld@dkfz.de
lab head
Sophia Foehr
contact affiliationDKFZ
contact emailsophia.foehr@dkfz.de
dataset submitter
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Dataset FTP location
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PRIDE project URI
Repository Record List
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