Figure 1.

Some aneuploidies and LOH events enable drug resistance. (a) Isochromosome (5 L) was detected in 12 fluconazole-resistant isolates from a survey of 90 clinical and laboratory isolates. Shown is comparative genome analysis performed with in-house produced microarrays [40] with the data displayed along the eight C. albicans chromosomes as log₂ ratios converted to ploidy levels (one, two, three or four gene copies) [40]. (b) Interpretation of i(5 L) geometry. CEN5 (magenta circle) maps to the breakpoint where extra copies of Chr5 L begin. Chr5 L includes ERG11, which encodes lanosterol 14-α-demethylase, the target of azole antifungals and TAC1, which encodes a transcription factor that positively regulates expression of efflux pump genes (CDR1 and CDR2). (c) The number of copies of ERG11 and TAC1-7 (a hyperactive allele of TAC1 [43]) correlate well with the level of resistance (MIC) of the strain as determined by deletion analysis of isogenic strains derived from parent strain carrying isochromosome (5 L) [34]. FLC, fluconazole.