PXD076200-1

PXD076200 is an original dataset announced via ProteomeXchange.

Title	Dipeptidyl peptidase IV contributes to the pathogenesis of Cryptococcus neoformans
Description	We previously identified isoleucine–proline–isoleucine (IPI) as a small molecule associated with extracellular vesicles (EVs) in Cryptococcus. The administration of IPI controlled experimental cryptococcal infection through mechanisms that remain unknown. IPI is an inhibitor of dipeptidyl peptidase 4 (DPP4), an enzyme that regulates insulin and glucose homeostasis in mammals and may also influence pathogenic processes in fungi. Based on these observations, we investigated the biological and pathogenic roles of cryptococcal DPP4. We demonstrate that Cryptococcus neoformans expresses an active, surface-associated DPP4 that is inhibited by IPI. Deletion of the DPP4-encoding gene (CNAG_06416) abolished DPP4 enzymatic activity and resulted in marked physiological alterations, including changes in the proteomic composition of whole cells and EVs, as well as increased accumulation of undivided cells at 37°C both in vitro and in vivo. The dpp4Δ mutant was less lethal than wild-type (WT) cells in a Galleria mellonella infection model. In contrast, increased DPP4 activity did not enhance lethality, as demonstrated by the ability of WT and 19 high–DPP4-expressing mutant strains to kill G. mellonella. In a murine model, loss of DPP4 significantly attenuated fungal virulence, delaying host mortality and reducing fungal burden, particularly in the brain. This finding is consistent with the observation that dpp4Δ cells were markedly less efficient at crossing endothelial and extracellular matrix layers than WT cells. Collectively, these findings establish DPP4 as an important regulator of cryptococcal physiology and pathogenesis, and support the concept that targeting DPP4 may offer translational opportunities distinct from conventional antifungal strategies.
HostingRepository	PRIDE
AnnounceDate	2026-07-17
AnnouncementXML	Submission_2026-07-17_09:08:18.961.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marlon D M Santos
SpeciesList	scientific name: Cryptococcus neoformans; NCBI TaxID: NCBITaxon:5207;
ModificationList	Carboxymethyl; Oxidation
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2026-03-26 12:21:54	ID requested
⏵ 1	2026-07-17 09:08:19	announced

Dataset with its publication pending

submitter keyword: None

Marcio L.
contact affiliation	Instituto Carlos Chagas, Fundação Oswaldo Cruz (Fiocruz), Curitiba, Brazil
contact email	marcio.rodrigues@fiocruz.br
lab head
Marlon D M Santos
contact affiliation	Computational Mass Spectrometry & Proteomics Group - Fiocruz
contact email	marlondms@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/2026/07/PXD076200

PRIDE project URI

• PRIDE
  1. PXD076200
     1. Label: PRIDE project
     2. Name: Dipeptidyl peptidase IV contributes to the pathogenesis of Cryptococcus neoformans