PXD052366-1

PXD052366 is an original dataset announced via ProteomeXchange.

Title	Disruption of ClpX reverts fluconazole susceptibility for Cryptococcus neoformans through modified heme biosynthesis and ergosterol production
Description	Fungal disease impacts the lives of almost a billion people across the globe. The opportunistic human fungal pathogen, Cryptococcus neoformans, causes cryptococcal meningitis in immunocompromised individuals with high fatality rates in response to limited treatment options. Moreover, the emergence of azole-resistant isolates in the clinic following prolonged treatment regimes, environmental fungicide exposure, and fungal evolution, threatens the outcome of current therapeutic options, endangering the survival of infected individuals. By quantitatively characterizing the proteomes of fluconazole-susceptible and -resistant C. neoformans strains using state-of-the-art tandem mass spectrometry, we defined ClpX, an ATP-dependent unfoldase, as a target to overcome resistance. We discovered that disruption of ClpX through deletion or inhibition re-introduces fluconazole susceptibility into the resistant strains, rendering treatment effective once again. We further explored the mechanism of susceptibility and determined interruption to heme biosynthesis and ergosterol production associated with ClpX. Our results contribute to the understanding of novel mechanisms driving fluconazole resistance and provide support for targeting proteins as a therapeutic strategy to combat resistance.
HostingRepository	PRIDE
AnnounceDate	2025-07-04
AnnouncementXML	Submission_2025-07-04_07:15:09.399.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Michael Woods
SpeciesList	scientific name: Fungi; NCBI TaxID: NCBITaxon:4751; scientific name: Cryptococcus neoformans var. grubii; NCBI TaxID: 178876;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-05-18 13:58:49	ID requested
⏵ 1	2025-07-04 07:15:09	announced

10.1038/S41467-025-61412-X;

submitter keyword: ClpX, Cryptococcus neoformans, ergosterol, heme,Antifungal resistance, quantitative proteomics, fluconazole

Jennifer Geddes-McAlister
contact affiliation	Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, Canada, N1G 2W1
contact email	jgeddesm@uoguelph.ca
lab head
Michael Woods
contact affiliation	Department of Molecular and Cellular Biology, University of Guelph
contact email	mwoods04@uoguelph.ca
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD052366
     1. Label: PRIDE project
     2. Name: Disruption of ClpX reverts fluconazole susceptibility for Cryptococcus neoformans through modified heme biosynthesis and ergosterol production