PXD040280

PXD040280 is an original dataset announced via ProteomeXchange.

Title	Vaginal epithelial dysfunction is mediated by the microbiome, metabolome, and mTOR signaling - Participant Group 2
Description	Bacterial vaginosis (BV) is characterized by depletion of Lactobacillus and overgrowth of anaerobic and facultative bacteria, leading to increased mucosal inflammation, epithelial disruption, and poor reproductive health outcomes. However, the molecular mediators contributing to vaginal epithelial dysfunction are poorly understood. Here we utilized proteomic, transcriptomic and metabolomic analyses to characterize biological features underlying BV in 405 African women and explored functional mechanisms using bacterial co-cultures in vitro. We identified five major vaginal microbiome groups, (L.crispatus(21%), L.iners(18%), any non-specific Lactobacillus species(9%), Gardnerella species .vaginalis(30%), or polymicrobial(22%)). Using multi-‘omics we show that BV associated epithelial disruption and mucosal inflammation are linked to the mammalian target of rapamycin (mTOR) pathway and associate with Gardnerella.vaginalis, Mobiluncus mulieris, and specific metabolites including imidazole propionate. Bacterial co-culture experiments in vitro confirmed that type strain G.vaginalis and, M.mulieris supernatants as well as imidazole propionate, directly affect epithelial barrier function and are accompanied by activation of mTOR pathways. These results establish the microbiome-mTOR axis as a central feature of epithelial dysfunction in BV.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:03:56.548.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Kenzie Birse
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2023-02-20 07:04:20	ID requested
1	2023-07-20 12:28:03	announced
⏵ 2	2023-11-14 09:03:57	announced	2023-11-14: Updated project metadata.

Berard AR, Brubaker DK, Birse K, Lamont A, Mackelprang RD, No, ë, l-Romas L, Perner M, Hou X, Irungu E, Mugo N, Knodel S, Muwonge TR, Katabira E, Hughes SM, Levy C, Calienes FL, Lauffenburger DA, Baeten JM, Celum C, Hladik F, Lingappa J, Burgener AD, Vaginal epithelial dysfunction is mediated by the microbiome, metabolome, and mTOR signaling. Cell Rep, 42(5):112474(2023) [pubmed]

submitter keyword: Human, LC-MSMS, Bacterial Vaginosis, Microbiome, Proteome

Adam Burgener
contact affiliation	Professor, Department of Pathology, School of Medicine Director, Center for Global Health and Diseases, School of Medicine, Case Western Reserve University 10900 Euclid Avenue, Cleveland, Ohio, 44106
contact email	adam.burgener@case.edu
lab head
Kenzie Birse
contact affiliation	University of Manitoba
contact email	kenzie.birse@umanitoba.ca
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/2023/07/PXD040280

PRIDE project URI

• PRIDE
  1. PXD040280
     1. Label: PRIDE project
     2. Name: Vaginal epithelial dysfunction is mediated by the microbiome, metabolome, and mTOR signaling - Participant Group 2