PXD043886-1

PXD043886 is an original dataset announced via ProteomeXchange.

Title	Pneumococcus suppresses host inflammatory response through COMMD2 mediated NF-κB degradation by aggrephagy
Description	NF-κB driven cellular immunity is essential for both pro- and anti-inflammatory responses to microbes, which makes it one of the most frequently targeted pathways by bacteria during pathogenesis. How NF-κB tunes the epithelial response to Streptococcus pneumoniae across the spectrum of commensal to pathogenic outcomes is not fully understood. In this study, we compare a commensal-like 6B ST90 strain to an invasive TIGR4 isolate and demonstrate that TIGR4 both blunts and antagonizes NF-κB activation. We identified, through comparative mass spectrometry of the p65 interactome, that the 6B ST90 isolate drives a non-canonical NF-κB RelB cascade, whereas TIGR4 induces p65 degradation though aggrephagy. Mechanistically, TIGR4 challenge triggers a novel interaction of COMMD2 with p65 and p62. This complex mediates export of p65 for degradation and is necessary for repressing host inflammatory transcription. With these results, we reveal for the first time a new bacterial pathogenesis mechanism to repress host inflammatory response though COMMD2 mediated turnover of p65, and present a paradigm for diverging NF-κB responses to pneumococcus.
HostingRepository	PRIDE
AnnounceDate	2026-09-07
AnnouncementXML	Submission_2026-09-06_16:17:38.749.xml
DigitalObjectIdentifier	https://doi.org/10.6019/PXD043886
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Michael Connor
SpeciesList	scientific name: Streptococcus pneumoniae TIGR4; NCBI TaxID: NEWT:170187;
ModificationList	phosphorylated residue; acetylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-18 22:44:25	ID requested
⏵ 1	2026-09-06 16:17:39	announced

10.6019/PXD043886;

Connor MG, Sanchez L, Chevalier C, Camarasa TMN, Carvalho F, Eldridge MJG, Chaze T, Matondo M, Karkeni E, Dufour S, Impens F, Baumgarten S, Enninga J, Hamon MA, Pneumococcus uses COMMD2 to alter host cellular immunity. Nat Commun, 17(1):(2026) [pubmed]

10.1038/s41467-026-72852-4;

submitter keyword: COMMD2, NF-κB degradation

Michael G. Connor
contact affiliation	Chromatin and Infection, Institut Pasteur, Paris, France.
contact email	mconnor@pasteur.fr
lab head
Michael Connor
contact affiliation	Institut Pasteur
contact email	mconnor@pasteur.fr
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/2026/09/PXD043886

PRIDE project URI

• PRIDE
  1. PXD043886
     1. Label: PRIDE project
     2. Name: Pneumococcus suppresses host inflammatory response through COMMD2 mediated NF-κB degradation by aggrephagy