PXD030631

PXD030631 is an original dataset announced via ProteomeXchange.

Title	OXSR1 inhibits inflammasome activation by limiting potassium efflux during mycobacterial infection
Description	Pathogenic mycobacteria inhibit inflammasome activation as part of their pathogenesis. While it is known that potassium efflux is a trigger for inflammasome activation, the interaction between mycobacterial infection, potassium efflux and inflammasome activation has not been investigated. Here we use Mycobacterium marinum infection of zebrafish embryos to demonstrate that pathogenic mycobacteria upregulate the host WNK signalling pathway kinases SPAK and OXSR1 which control intracellular potassium balance. We show that genetic depletion or inhibition of OXSR1 decreases bacterial burden and intracellular potassium levels. The protective effects of OXSR1 depletion are mediated by NLRP3 inflammasome activation and are dependent on caspase-mediated release of IL-1β and the downstream activation of protective TNF-α. The elucidation of this druggable pathway to potentiate inflammasome activation provides a new avenue for the development of host-directed therapies against intracellular infections.
HostingRepository	PRIDE
AnnounceDate	2022-05-05
AnnouncementXML	Submission_2022-05-05_00:53:50.047.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	matthew O'Rourke
SpeciesList	scientific name: Mycobacterium marinum; NCBI TaxID: 1781; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-12-24 00:35:09	ID requested
⏵ 1	2022-05-05 00:53:50	announced

Dataset with its publication pending

submitter keyword: Human, Cell lines, LCMS, Mycobacterium

Stefan H Oehlers
contact affiliation	1. Tuberculosis Research Program Centenary Institute, The University of Sydney, Camperdown, NSW 2050, Australia 2. The University of Sydney, Discipline of Infectious Diseases & Immunology and Sydney Institute for Infectious Diseases, Camperdown, NSW 2050, Australia
contact email	matthew.orourke@uts.edu.au
lab head
matthew O'Rourke
contact affiliation	University of Sydney
contact email	matthew.orourke1@gmail.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/2022/05/PXD030631

PRIDE project URI

• PRIDE
  1. PXD030631
     1. Label: PRIDE project
     2. Name: OXSR1 inhibits inflammasome activation by limiting potassium efflux during mycobacterial infection