PXD057289

PXD057289 is an original dataset announced via ProteomeXchange.

Title	Inflammasome-independent IL-1β activation via staphopain A protease of Staphylococcus aureus
Description	Interleukin-1β (IL-1β) is a pivotal mediator of innate immunity, essential for orchestrating the acute inflammatory response. While the canonical activation of IL-1β involves cleavage of its inactive precursor (pro-IL-1β) by the inflammatory cysteine protease caspase-1, certain bacterial proteases, such as those secreted by group A Streptococcus and Pseudomonas aeruginosa, can also activate pro-IL-1β. In this study, we demonstrate that infection of human N/TERT-1 immortalized keratinocytes by Staphylococcus aureus induces IL-1β processing independently of the classical inflammasome pathways. Biochemical analysis reveals that a secreted factor from S. aureus cleaves pro-IL-1β at a site proximal to the canonical caspase-1 cleavage site, rendering the cytokine bioactive. Specifically, we identify the secreted cysteine protease staphopain A as responsible for this cleavage. Our findings highlight a novel mechanism of inflammasome-independent IL-1β activation through microbial proteases, expanding the understanding of pathogen-host interactions in immune responses, specifically in the skin.
HostingRepository	PRIDE
AnnounceDate	2025-10-27
AnnouncementXML	Submission_2025-10-26_17:04:31.117.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mario Oroshi
SpeciesList	scientific name: Staphylococcus aureus; NCBI TaxID: NEWT:1280;
ModificationList	No PTMs are included in the dataset
Instrument	Bruker Daltonics micrOTOF series

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-29 07:19:08	ID requested
⏵ 1	2025-10-26 17:04:32	announced

10.1016/j.jbc.2025.110574;

Bauernfried S, Komar T, Sterle K, Tanzer MC, Horswill AR, Mann M, Hornung V, activation via staphopain A protease of Staphylococcus aureus. J Biol Chem, 301(10):110574(2025) [pubmed]

submitter keyword: keratinocytes, inflammasome,Interleukin-1β, staphopain A, Staphylococcus aureus, microbial proteases, NLRP1

Veit Hornung
contact affiliation	Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany
contact email	hornung@genzentrum.lmu.de
lab head
Mario Oroshi
contact affiliation	Proteomics
contact email	oroshi@biochem.mpg.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/2025/10/PXD057289

PRIDE project URI

• PRIDE
  1. PXD057289
     1. Label: PRIDE project
     2. Name: Inflammasome-independent IL-1β activation via staphopain A protease of Staphylococcus aureus