The zinc cluster transcription factor Znc1 regulates Rta3-dependent miltefosine resistance in .

Unlabelled: Zinc cluster transcription factors (ZCFs) are a family of transcription regulators that are almost exclusively found in the fungal kingdom. Activating mutations in the ZCFs Mrr1, Tac1, and Upc2 frequently cause acquired resistance to the widely used antifungal drug fluconazole in the pathogenic yeast . Similar to a hyperactive Tac1, a constitutively active form of the ZCF Znc1 causes increased fluconazole resistance by upregulating the multidrug efflux pump-encoding gene .

Multiple phosphorylation sites regulate the activity of the repressor Mig1 in .

The SNF1 protein kinase signaling pathway, which is highly conserved in eukaryotic cells, is important for metabolic adaptations in the pathogenic yeast . However, so far, it has remained elusive how SNF1 controls the activity of one of its main effectors, the repressor protein Mig1 that inhibits the expression of genes required for the utilization of alternative carbon sources when glucose is available. In this study, we have identified multiple phosphorylation sites in Mig1 that contribute to its inactivation.

The Ypk1 protein kinase signaling pathway is rewired and not essential for viability in Candida albicans.

Protein kinases are central components of almost all signaling pathways that control cellular activities. In the model organism Saccharomyces cerevisiae, the paralogous protein kinases Ypk1 and Ypk2, which control membrane lipid homeostasis, are essential for viability, and previous studies strongly indicated that this is also the case for their single ortholog Ypk1 in the pathogenic yeast Candida albicans. Here, using FLP-mediated inducible gene deletion, we reveal that C.

Generation of Viable Candida albicans Mutants Lacking the "Essential" Protein Kinase Snf1 by Inducible Gene Deletion.

The protein kinase Snf1, a member of the highly conserved AMP-activated protein kinase family, is a central regulator of metabolic adaptation. In the pathogenic yeast , Snf1 is considered to be essential, as previous attempts by different research groups to generate homozygous Δ mutants were unsuccessful. We aimed to elucidate why Snf1 is required for viability in by generating Δ null mutants through forced, inducible gene deletion and observing the terminal phenotype before cell death.

Evolution of Fluconazole-Resistant Candida albicans Strains by Drug-Induced Mating Competence and Parasexual Recombination.

The clonal population structure of suggests that (para)sexual recombination does not play an important role in the lifestyle of this opportunistic fungal pathogen, an assumption that is strengthened by the fact that most strains are heterozygous at the mating type locus () and therefore mating-incompetent. On the other hand, mating might occur within clonal populations and allow the combination of advantageous traits that were acquired by individual cells to adapt to adverse conditions. We have investigated if parasexual recombination may be involved in the evolution of highly drug-resistant strains exhibiting multiple resistance mechanisms against fluconazole, an antifungal drug that is commonly used to treat infections by Growth of strains that were heterozygous for and different fluconazole resistance mutations in the presence of the drug resulted in the emergence of derivatives that had become homozygous for the mutated allele and the mating type locus and exhibited increased drug resistance.