Transposon-sequencing (Tn-seq) of the Candida glabrata reference strain CBS138 reveals epigenetic plasticity, structural variation, and intrinsic mechanisms of resistance to micafungin.

Candida glabrata (also called Nakaseomyces glabratus) is an opportunistic pathogen that can resist common antifungals and rapidly acquire multidrug resistance. A large amount of genetic variation exists between isolates, which complicates generalizations. Portable transposon-sequencing (Tn-seq) methods can efficiently provide genome-wide information on strain differences and genetic mechanisms.

Calcineurin-dependent contributions to fitness in the opportunistic pathogen .

The protein phosphatase calcineurin is vital for the virulence of the opportunistic fungal pathogen . The host-induced stresses that activate calcineurin signaling are unknown, as are the targets of calcineurin relevant to virulence. To potentially shed light on these processes, millions of transposon insertion mutants throughout the genome of were profiled for fitness defects in the presence of FK506, a specific inhibitor of calcineurin.

Redefining pleiotropic drug resistance in a pathogenic yeast: Pdr1 functions as a sensor of cellular stresses in .

is a prominent opportunistic fungal pathogen of humans. The increasing incidence of infections is attributed to both innate and acquired resistance to antifungals. Previous studies suggest the transcription factor Pdr1 and several target genes encoding ABC transporters are critical elements of pleiotropic defense against azoles and other antifungals.

Redefining Pleiotropic Drug Resistance in a Pathogenic Yeast: Pdr1 Functions as a Sensor of Cellular Stresses in .

Unlabelled: is a prominent opportunistic fungal pathogen of humans. The increasing incidence of infections is attributed to both innate and acquired resistance to antifungals. Previous studies suggest the transcription factor Pdr1 and several target genes encoding ABC transporters are critical elements of pleiotropic defense against azoles and other antifungals.

Genome and transcriptome of a pathogenic yeast, Candida nivariensis.

We present a highly contiguous genome and transcriptome of the pathogenic yeast, Candida nivariensis. We sequenced both the DNA and RNA of this species using both the Oxford Nanopore Technologies and Illumina platforms. We assembled the genome into an 11.

Identification of Essential Genes and Fluconazole Susceptibility Genes in by Profiling Transposon Insertions.

Within the budding yeasts, the opportunistic pathogen and other members of the clade have developed virulence traits independently from and To begin exploring the genetic basis of virulence and its innate resistance to antifungals, we launched the transposon from a plasmid and sequenced more than 500,000 different semi-random insertions throughout the genome. With machine learning, we identified 1278 protein-encoding genes (25% of total) that could not tolerate transposon insertions and are likely essential for fitness Interestingly, genes involved in mRNA splicing were less likely to be essential in than their orthologs in , whereas the opposite is true for genes involved in kinetochore function and chromosome segregation. When a pool of insertion mutants was challenged with the first-line antifungal fluconazole, insertions in several known resistance genes (, , , , , , , ) and 15 additional genes (including , , ) became hypersensitive to fluconazole.

Comparing the utility of in vivo transposon mutagenesis approaches in yeast species to infer gene essentiality.

In vivo transposon mutagenesis, coupled with deep sequencing, enables large-scale genome-wide mutant screens for genes essential in different growth conditions. We analyzed six large-scale studies performed on haploid strains of three yeast species (Saccharomyces cerevisiae, Schizosaccaromyces pombe, and Candida albicans), each mutagenized with two of three different heterologous transposons (AcDs, Hermes, and PiggyBac). Using a machine-learning approach, we evaluated the ability of the data to predict gene essentiality.

Auxin-Inducible Depletion of the Essentialome Suggests Inhibition of TORC1 by Auxins and Inhibition of Vrg4 by SDZ 90-215, a Natural Antifungal Cyclopeptide.

Gene knockout and knockdown strategies have been immensely successful probes of gene function, but small molecule inhibitors (SMIs) of gene products allow much greater time resolution and are particularly useful when the targets are essential for cell replication or survival. SMIs also serve as lead compounds for drug discovery. However, discovery of selective SMIs is costly and inefficient.

Chryseobacterium angstadtii sp. nov., isolated from a newt tank.

As part of an undergraduate microbiology course, a yellow-orange-pigmented, Gram-staining negative, rod-shaped, non-motile bacterial strain was isolated from a glass tank housing several red-spotted newts (Notophthalmus viridescens). The sequence of the 16S rRNA gene of this strain, designated KM(T), was 97.4-98.