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Fungus Genome Fluctuates to Confer Drug Resistance

Candida albicans shifts gene copy number to allow resistance to common antifungal agents

FRIDAY, July 21 (HealthDay News) -- When Candida albicans develops drug resistance, if often does so by increasing the number of full or segmented chromosomes, possibly because aneuploidy increases the dosage of drug resistance genes, according to a report published in the July 21 issue of Science.

To understand how genome plasticity might facilitate drug resistance, Judith Berman, Ph.D., from the University of Minnesota in Minneapolis, and colleagues measured the copy number of genes found in 70 azole-sensitive and azole-resistant C. albicans strains.

Twenty-three of the strains had an abnormal number of chromosomes or chromosomal segments, called isochromosomes. Aneuploidy was seven times as prevalent in fluconazole-resistant strains than in fluconazole-sensitive ones, and many of the resistant strains carried an isochromosome with fragments from chromosome 5. This region was found to harbor genes responsible for drug resistance including drug pumps and their transcription factors, and an enzyme in the ergosterol pathway targeted by azoles.

The authors believe that C. albicans will be a useful model for studying isochromosome formation. Furthermore, they said, "Reagents that reduce chromosome breakage and/or recombination events resulting in isochromosome formation could be useful companions to current azole antifungal treatments."

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