| | Category | MI | L20 | Multidrug Resistance: C. albicans Gene IPT1 Affects Gene |
| | Expression |
| | Abstract | Candida albicans is the most commonly isolated yeast in human disease; it |
| | acutely impacts immunocompromised patients. Furthermore, C. albicans |
| | resistance to antifungal drugs is escalating. The purpose of this |
| | investigation was to determine which C. albicans genes in the target |
| | pathways of the antifungal drugs: aureobasidin, rapamycin, and |
| | fluvastatin are affected by transformation with high copy number plasmids |
| | containing the gene IPT1. The two transformants and the controls were |
| | cultured and tested on ten antifungal drugs at five concentrations, and the |
| | transformants were proven resistant to nine of these drugs. RNA was |
| | isolated from the transformants at 4 time intervals with exposure to three |
| | drugs and no drug. Total mRNA was reverse transcribed into cDNA, |
| | which was then quantified by real-time PCR. Levels of transcription of IPT1 |
| | and of genes known to affect drug resistance were determined, including |
| | AUR1 (aureobasidin A), HMG1 (fluvastatin), and TOR (rapamycin), and |
| | known drug efflux genes (CDR1 and MDR1). Data indicated that |
| | expression of the cloned IPT1 was not necessary for resistance, |
| | suggesting that DNA sequences are directly altering phenotype, perhaps |
| | by sequestering regulatory proteins. Genomic DNA agarose gel analysis |
| | revealed that one plasmid had a rearranged version of IPT1 and both |
| | plasmids had an insert. The observed changes in expression likely cause |
| | the multidrug resistance and occur because of integrative disruption of |
| | chromosomal IPT1 by the homologous sequences in the plasmid. Multidrug |
| | resistance suggests that there are regulatory links between unrelated |
| | pathways that can be utilized for drug development. |
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