Y132F + K143R (double mutant)

Synergistic effect is that the strongest increases observed in many functional assays and allele-swap experiments — reported as the largest fluconazole MIC increases of any tested allele (often >64–>128-fold). Flowers et al. demonstrated the Y132F+K143R double allele produced the largest MIC rise of alleles tested.

Produces markedly elevated voriconazole MICs (often several-fold higher than either single substitution alone; reported MICs in resistant isolates commonly ≥2–8 µg/mL or greater).

Documented in clinical isolates and in experimental allele-swap studies; double mutants are of special clinical concern because they generate high-level cross-resistance to multiple azoles.

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