Gene expression and evolution of antifungal drug resistance. 2009

James B Anderson, and Caroline Sirjusingh, and Nazia Syed, and Shantelle Lafayette
Department of Cell and Systems Biology, University of Toronto, 3359 Mississauga Road North, Mississauga, Ontario L5L 1C6, Canada. jb.anderson@utoronto.ca

Permanent changes in gene expression result from certain forms of antifungal resistance. In this study, we asked whether any changes in gene expression are required for the evolution of a drug-resistant phenotype in populations. We examined the changes in gene expression resulting from the evolution of resistance in experimental populations of the yeast Saccharomyces cerevisiae with two antifungal drugs, fluconazole (FLC) in a previous study and amphotericin B (AmB) in this study, in which five populations were subjected to increasing concentrations of AmB, from 0.25 to 128 microg/ml in twofold increments. Six genes, YGR035C, YOR1, ICT1, GRE2, PDR16, and YPLO88W, were consistently overexpressed with resistance to AmB reported here and with resistance to FLC involving a mechanism of increased efflux reported previously. We then asked if the deletion of these genes impaired the ability of populations to evolve resistance to FLC over 108 generations of asexual reproduction in 32 and 128 microg/ml FLC, the same conditions under which FLC-resistant types evolved originally. For each of three deletion strains, YOR1, ICT1, and PDR16 strains, extinctions occurred in one of two replicate populations growing in 128 microg/ml FLC. Each of these three deletion strains was mixed 1:1 with a marked version of the wild type to measure the relative ability of the deletion strain to adapt over 108 generations. In these assays, only the PDR16 deletion strain consistently became extinct both at 32 and at 128 microg/ml FLC. The deletion of PDR16 reduces the capacity of a population to evolve to resistance to FLC.

UI MeSH Term Description Entries
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D000666 Amphotericin B Macrolide antifungal antibiotic produced by Streptomyces nodosus obtained from soil of the Orinoco river region of Venezuela. Amphocil,Amphotericin,Amphotericin B Cholesterol Dispersion,Amphotericin B Colloidal Dispersion,Fungizone
D000935 Antifungal Agents Substances that destroy fungi by suppressing their ability to grow or reproduce. They differ from FUNGICIDES, INDUSTRIAL because they defend against fungi present in human or animal tissues. Anti-Fungal Agents,Antifungal Agent,Fungicides, Therapeutic,Antibiotics, Antifungal,Therapeutic Fungicides,Agent, Antifungal,Anti Fungal Agents,Antifungal Antibiotics
D012441 Saccharomyces cerevisiae A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement. Baker's Yeast,Brewer's Yeast,Candida robusta,S. cerevisiae,Saccharomyces capensis,Saccharomyces italicus,Saccharomyces oviformis,Saccharomyces uvarum var. melibiosus,Yeast, Baker's,Yeast, Brewer's,Baker Yeast,S cerevisiae,Baker's Yeasts,Yeast, Baker
D015725 Fluconazole Triazole antifungal agent that is used to treat oropharyngeal CANDIDIASIS and cryptococcal MENINGITIS in AIDS. Apo-Fluconazole,Béagyne,Diflucan,Fluc Hexal,FlucoLich,Flucobeta,Fluconazol AL,Fluconazol AbZ,Fluconazol Stada,Fluconazol von ct,Fluconazol-Isis,Fluconazol-ratiopharm,Flunazul,Fungata,Lavisa,Loitin,Neofomiral,Oxifungol,Solacap,Triflucan,UK-49858,Zonal,Apo Fluconazole,Fluconazol Isis,Fluconazol ratiopharm,UK 49858,UK49858
D015966 Gene Expression Regulation, Fungal Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in fungi. Fungal Gene Expression Regulation,Regulation of Gene Expression, Fungal,Regulation, Gene Expression, Fungal
D019143 Evolution, Molecular The process of cumulative change at the level of DNA; RNA; and PROTEINS, over successive generations. Molecular Evolution,Genetic Evolution,Evolution, Genetic
D020411 Oligonucleotide Array Sequence Analysis Hybridization of a nucleic acid sample to a very large set of OLIGONUCLEOTIDE PROBES, which have been attached individually in columns and rows to a solid support, to determine a BASE SEQUENCE, or to detect variations in a gene sequence, GENE EXPRESSION, or for GENE MAPPING. DNA Microarrays,Gene Expression Microarray Analysis,Oligonucleotide Arrays,cDNA Microarrays,DNA Arrays,DNA Chips,DNA Microchips,Gene Chips,Oligodeoxyribonucleotide Array Sequence Analysis,Oligonucleotide Microarrays,Sequence Analysis, Oligonucleotide Array,cDNA Arrays,Array, DNA,Array, Oligonucleotide,Array, cDNA,Arrays, DNA,Arrays, Oligonucleotide,Arrays, cDNA,Chip, DNA,Chip, Gene,Chips, DNA,Chips, Gene,DNA Array,DNA Chip,DNA Microarray,DNA Microchip,Gene Chip,Microarray, DNA,Microarray, Oligonucleotide,Microarray, cDNA,Microarrays, DNA,Microarrays, Oligonucleotide,Microarrays, cDNA,Microchip, DNA,Microchips, DNA,Oligonucleotide Array,Oligonucleotide Microarray,cDNA Array,cDNA Microarray
D020869 Gene Expression Profiling The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell. Gene Expression Analysis,Gene Expression Pattern Analysis,Transcript Expression Analysis,Transcriptome Profiling,Transcriptomics,mRNA Differential Display,Gene Expression Monitoring,Transcriptome Analysis,Analyses, Gene Expression,Analyses, Transcript Expression,Analyses, Transcriptome,Analysis, Gene Expression,Analysis, Transcript Expression,Analysis, Transcriptome,Differential Display, mRNA,Differential Displays, mRNA,Expression Analyses, Gene,Expression Analysis, Gene,Gene Expression Analyses,Gene Expression Monitorings,Gene Expression Profilings,Monitoring, Gene Expression,Monitorings, Gene Expression,Profiling, Gene Expression,Profiling, Transcriptome,Profilings, Gene Expression,Profilings, Transcriptome,Transcript Expression Analyses,Transcriptome Analyses,Transcriptome Profilings,mRNA Differential Displays
D025141 Drug Resistance, Fungal The ability of fungi to resist or to become tolerant to chemotherapeutic agents, antifungal agents, or antibiotics. This resistance may be acquired through gene mutation. Antibiotic Resistance, Fungal,Antifungal Drug Resistance,Resistance, Antifungal Drug

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