Micafungin is not an efflux pump substrate

抄録

The micafungin and caspofungin susceptibilities of Saccharomyces cerevisiae strains stably hyper-expressing fungal ATP-binding cassette (ABC) or major facilitator super-family (MFS) transporters were determined using three separate methods: agar plate drug resistance, liquid microdilution susceptibility, and agar diffusion assays. Strains hyper-expressing individual alleles of ABC transporters or an MFS transporter gave the expected resistance profiles for the azoles fluconazole, itraconazole and voriconazole. The strains hyper-expressing CDR2 showed a slightly decreased susceptibility to caspofungin in agar plate drug resistance assays, as previously reported, but increased susceptibility to micafungin compared with either the strains hyper-expressing CDR1 or the null parent deleted of seven ABC transporters. The strains hyper-expressing CDR1 showed slightly decreased susceptibility to micafungin in these assays. These effects occurred within narrow ranges of candin concentration but they did not translate to other assays. None of the strains showed significant resistance to micafungin or caspofungin in liquid microdilution susceptibility assays. The strains hyper-expressing transporters and the null parent had micafungin MICs of 0.125 -0.25 μg/ml, and caspofungin MICs of 1.0-2.0 μg/ml. The antifungal activity of micafungin and caspofungin were similar in agarose diffusion assays, although the shape and size of the caspofungin inhibitory zones were affected by medium composition. The potency of micafungin and caspofungin are assay dependent but neither candin appears to be a substrate of fungal ABC or MFS transporters.