PXD047041

PXD047041 is an original dataset announced via ProteomeXchange.

Title	Proteomics reveals that the antifungal activity of fenbendazole against Cryptococcus neoformans requires protein kinases.
Description	Cryptococcus neoformans is responsible for over 100,000 deaths annually, and the treatment of this fungal disease is expensive and not consistently effective. Unveiling new therapeutic avenues is crucial. Previous studies have suggested that the anthelmintic drug fenbendazole is an affordable and non-toxic candidate to combat cryptococcosis. However, its mechanism of anticryptococcal activity has been only superficially investigated. In this study, we examined the global cellular response of C. neoformans to fenbendazole using a proteomic approach. Fenbendazole treatment mostly impacted the abundance of proteins related to metabolic pathways, RNA processing, and intracellular traffic. Protein kinases, in particular, were significantly affected by fenbendazole treatment. Experimental validation of the proteomics data using a collection of C. neoformans mutants led to the identification of critical roles of five protein kinases in fenbendazole's antifungal activity. In fact, mutants lacking the expression of genes encoding Chk1, Tco2, Tco3, Bub1, and Sch9 kinases demonstrated greater resistance to fenbendazole compared to wild-type cells. In combination with the standard antifungal drug amphotericin B, fenbendazole reduced the cryptococcal burden in mice. These findings not only contribute to the elucidation of fenbendazole's mode of action but also support its use in combination therapy with amphotericin B. In conclusion, our data suggest that fenbendazole holds promise for further development as an anticryptococcal agent.
HostingRepository	PRIDE
AnnounceDate	2024-05-21
AnnouncementXML	Submission_2024-05-21_11:22:08.445.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marlon D M Santos
SpeciesList	scientific name: Cryptococcus neoformans var. grubii serotype A (strain H99 / ATCC 208821 / CBS 10515 / FGSC 9487) (Filobasidiella neoformans var. grubii); NCBI TaxID: 235443;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-11-17 09:45:04	ID requested
⏵ 1	2024-05-21 11:22:11	announced

10.1016/j.ijantimicag.2024.107157;

de Oliveira HC, Santos MDM, Camillo-Andrade AC, Castelli RF, Dos Reis FCG, Carvalho PC, Rodrigues ML, Proteomics reveals that the antifungal activity of fenbendazole against Cryptococcus neoformans requires protein kinases. Int J Antimicrob Agents, 63(5):107157(2024) [pubmed]

submitter keyword: Cryptococcus neoformans

antifungal activity

fenbendazole

proteomics

protein kinases

Marcio L Rodrigues
contact affiliation	Instituto Carlos Chagas, Fundação Oswaldo Cruz (Fiocruz), Curitiba, Brazil.
contact email	marciolrodrig@gmail.com
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/2024/05/PXD047041

PRIDE project URI

• PRIDE
  1. PXD047041
     1. Label: PRIDE project
     2. Name: Proteomics reveals that the antifungal activity of fenbendazole against Cryptococcus neoformans requires protein kinases.