PXD078067-1

PXD078067 is an original dataset announced via ProteomeXchange.

Title	Candida glabrata YPK2 is a multidrug susceptibility locus
Description	The biological conservation between fungi and mammals has made development of selective antifungal drugs a difficult challenge. Further complicating this situation is the selection of antifungal drug-resistant organisms during drug treatment. The pathogenic yeast Nakaseomyces glabratus (called here Candida glabrata) presents an especially challenging organism due to its tendency to frequently lose susceptibility to the major antifungal drug class the azoles. Additionally, C. glabrata develops resistance to echinocandin drugs, a second, more recently described antifungal agent at 10 times the rate of other organisms. Previous work has established that the sterol responsive transcriptional regulator Upc2A is a key determinant of azole susceptibility in C. glabrata and plays a role in echinocandin resistance. We used a biochemical approach to identify proteins that co-purified with Upc2A and identified the Ypk2 AGC kinase as an interacting protein. Strains lacking YPK2 exhibited increased susceptibility to fluconazole and the echinocandin caspofungin. A ypk2 strain failed to normally induce transcription of several ERG genes but exhibited normal induction of the CDR1 ATP-binding cassette transporter gene. Isogenic ypk2 strains were also highly susceptible to the three major classes of antifungal drugs, indicating that this kinase behaves as a multidrug susceptibility factor. RNA-seq analyses indicated that the transcriptional response to exposure is different for each drug and each response is differentially altered upon loss of Ypk2. Our data indicate that Ypk2 plays an important role coordinating gene expression that impacts susceptibility to all major antifungal drug classes.
HostingRepository	PRIDE
AnnounceDate	2026-07-07
AnnouncementXML	Submission_2026-07-07_03:59:52.009.xml
DigitalObjectIdentifier	https://doi.org/10.6019/PXD078067
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Thomas Krüger
SpeciesList	scientific name: [Candida] glabrata CBS 138; NCBI TaxID: NEWT:284593;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2026-05-06 03:31:29	ID requested
⏵ 1	2026-07-07 03:59:52	announced

10.6019/PXD078067;

submitter keyword: Candida glabrata, Upc2A, YPK2 AGC kinase, RNA-seq, fluconazole

Axel A. Brakhage
contact affiliation	Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute Jena, Leibniz-HKI, Jena
contact email	axel.brakhage@leibniz-hki.de
lab head
Thomas Krüger
contact affiliation	Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute
contact email	thomas.krueger@leibniz-hki.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD078067
     1. Label: PRIDE project
     2. Name: Candida glabrata YPK2 is a multidrug susceptibility locus