PXD071991-1

PXD071991 is an original dataset announced via ProteomeXchange.

Title	p38 MAPK and MDT-15 Mediate SKN-1–Dependent Metformin-Induced Protection Against Mitis Group Streptococci in Caenorhabditis elegans
Description	Mitis group streptococci are opportunistic pathogens residing in the oral cavity, where they produce hydrogen peroxide (H2O2), a key virulence factor contributing to their pathogenesis. We previously demonstrated that these bacteria kill the nematode Caenorhabditis elegans through H2O2 production. Metformin, a widely used biguanide drug for managing blood glucose levels, has shown promising effects on aging by extending lifespan in worms and mice, and has also demonstrated potential cancer treatment. Additionally, pretreatment with metformin enhances the survival of worms and triggers an immune response via the p38 MAPK pathway against various pathogenic bacteria. Based on these observations, we investigated metformin's potential as a therapeutic agent against mitis group streptococcal infections and its underlying mechanisms in the current study. Pretreatment of worms with metformin provided significant dose-dependent protection from streptococcal-derived H2O2. This protective effect was attributed to the activation of the oxidative stress response transcription factor SKN-1/NRF2. Further analysis revealed that the p38 MAPK pathway and the transcription mediator complex protein MDT-15 are essential for the activation of SKN-1 by metformin. Interestingly, SKN-1 activity, mediated by MDT-15, was found to be independent of the p38 MAPK pathway. Our findings establish that metformin-mediated protection against mitis group streptococcal infections relies on the coordinated action of SKN-1, the p38 MAPK pathway, and MDT-15. These insights suggest that metformin could be a valuable therapeutic agent in combating these infections. Future research should focus on further elucidating the molecular mechanisms involved and exploring the potential clinical applications of metformin in treating these bacterial infections.
HostingRepository	PRIDE
AnnounceDate	2026-08-07
AnnouncementXML	Submission_2026-08-07_11:23:36.465.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ransome van der Hoeven
SpeciesList	scientific name: Caenorhabditis elegans; NCBI TaxID: NEWT:6239;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Astral

Revision	Datetime	Status	ChangeLog Entry
0	2025-12-14 21:08:22	ID requested
⏵ 1	2026-08-07 11:23:37	announced

Al Hatem A, Balasubramaniam B, Villhauer A, Naji AK, van der Hoeven R, p38 MAPK and MDT-15 mediate SKN-1-dependent metformin-induced protection against mitis group streptococci in Caenorhabditis elegans. Geroscience, ():(2026) [pubmed]

10.1007/s11357-026-02405-6;

submitter keyword: None

Ransome van
contact affiliation	Associate Professor Iowa Institute for Oral Health Research Department of Periodontics University of Iowa College of Dentistry and Dental Clinics N423 Dental Science Building 801 Newton Rd, Iowa City, IA 52242
contact email	ransome-vanderhoeven@uiowa.edu
lab head
Ransome van der Hoeven
contact affiliation	Associate Professor Iowa Institute for Oral Health Research Department of Periodontics University of Iowa College of Dentistry and Dental Clinics N423 Dental Science Building 801 Newton Rd Iowa City, IA - 52242
contact email	ransome-vanderhoeven@uiowa.edu
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/2026/08/PXD071991

PRIDE project URI

• PRIDE
  1. PXD071991
     1. Label: PRIDE project
     2. Name: p38 MAPK and MDT-15 Mediate SKN-1–Dependent Metformin-Induced Protection Against Mitis Group Streptococci in Caenorhabditis elegans