Overexpression of Candida albicans CDR1, CDR2, or MDR1Does Not Produce Significant Changes in Echinocandin Susceptibility

Autor: Niimi, K., Maki, K., Ikeda, F., Holmes, A. R., Lamping, E., Niimi, M., Monk, B. C., Cannon, R. D.
Zdroj: Antimicrobial Agents and Chemotherapy; April 2006, Vol. 50 Issue: 4 p1148-1155, 8p
Abstrakt: ABSTRACTThe micafungin and caspofungin susceptibilities of Candida albicanslaboratory and clinical isolates and of Saccharomyces cerevisiaestrains stably hyperexpressing fungal ATP-binding cassette (ABC) or major facilitator superfamily (MFS) transporters involved in azole resistance were determined using three separate methods. Yeast strains hyperexpressing individual alleles of ABC transporters or an MFS transporter from C. albicansgave the expected resistance profiles for the azoles fluconazole, itraconazole, and voriconazole. The strains hyperexpressing CDR2showed slightly decreased susceptibility to caspofungin in agar plate drug resistance assays, as previously reported, but increased susceptibility to micafungin compared with either the strains hyperexpressing CDR1or the null parent deleted of seven ABC transporters. The strains hyperexpressing CDR1showed slightly decreased susceptibility to micafungin in these assays. A C. albicansclinical isolate overexpressing both Cdr1p and Cdr2p relative to its azole-sensitive isogenic progenitor acquired resistance to azole drugs and showed reduced susceptibility to caspofungin and slightly increased susceptibility to micafungin in agar plate drug resistance assays. None of the strains showed significant resistance to micafungin or caspofungin in liquid microdilution susceptibility assays. The antifungal activities 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 assessment of micafungin and caspofungin potency is therefore assay dependent; the differences seen with agar plate drug resistance assays occur over narrow ranges of echinocandin concentrations and are not of clinical significance.
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