Project description:Transcriptomic responses of Candida glabrata strains, BG2 and CBS138, to two azole antifungal drugs, Fluconazole and Voriconazole.

2025-07-29 | GSE273379 | GEO

A ceramide synthase is important for filamentous fungal biofilm morphology and antifungal drug susceptibility

Project description:The complex structure of the biofilm generates microenvironments which impact the fitness of the biofilm community as a whole. Contributions to fitness include the development of emergent properties resulting in the recalcitrance to external stressors such as environmental stress or drug stress in the context of a pathogen. The biofilm developed by the filamentous fungal pathogen Aspergillus fumigatus develops zones of low oxygen which contribute to a reduction in antifungal drug susceptibility, however the mechanisms driving this have remained elusive. Here we have utilized a transcriptomic approach to probe the biofilm structure in comparison to a planktonic lifestyle to identify unique biofilm transcriptional patterns. Importantly we utilized two phenotypically diverse strains. From this analysis we have identified biofilm specific gene co-expression networks as well as a ceramide synthase, designated barA, with a striking increase in transcript abundance specifically in the biofilm. Null mutants for barA in two strain backgrounds display altered biofilm morphology with some strain specific differences but interestingly do not impact virulence. Importantly we find the BarA ceramide synthase has a role in regulating susceptibility to classes of ergosterol targeting antifungal drugs. In the absence of barA, treatment with voriconazole leads to significant cellular damage in the form of lysis. Through this we have identified a novel mechanism driving antifungal drug resistance in the biofilm of filamentous fungal pathogen.

2026-05-01 | GSE325906 | GEO

Antifungal susceptibility profiles and drug resistance mechanisms of clinical <i>Candida duobushaemulonii</i> isolates from China.

Project description: Not available

| S-EPMC9760970 | biostudies-literature

Candida glabrata YPK2 is a multidrug susceptibility locus

Project 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.

2026-07-07 | PXD078067 | Pride

Candida glabrata YPK2 is a multidrug susceptibility locus

Project description:The biological conservation between fungi and mammals due to a common ancestor 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 ypk2D strain failed to normally induce transcription of several ERG genes but exhibited normal induction of the CDR1 ATP-binding cassette transporter gene. Isogenic ypk2D 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 in coordinating gene expression that impacts susceptibility to all major antifungal drug classes.

2026-07-06 | GSE334456 | GEO

Candida auris Clinical Isolates from South Korea: Identification, Antifungal Susceptibility, and Genotyping.

Project description: Not available

| S-EPMC6440790 | biostudies-literature