Niimi K, Maki K, Ikeda F, Holmes A R, Lamping E, Niimi M, Monk B C, Cannon R D
Department of Oral Sciences, University of Otago, P.O. Box 647, 310 Great King Street, Dunedin, New Zealand.
Antimicrob Agents Chemother. 2006 Apr;50(4):1148-55. doi: 10.1128/AAC.50.4.1148-1155.2006.
The micafungin and caspofungin susceptibilities of Candida albicans laboratory and clinical isolates and of Saccharomyces cerevisiae strains 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. albicans gave the expected resistance profiles for the azoles fluconazole, itraconazole, and voriconazole. The strains hyperexpressing CDR2 showed 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 CDR1 or the null parent deleted of seven ABC transporters. The strains hyperexpressing CDR1 showed slightly decreased susceptibility to micafungin in these assays. A C. albicans clinical 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.
采用三种不同方法，测定了白色念珠菌实验室菌株和临床分离株以及稳定高表达参与唑类耐药的真菌ATP结合盒（ABC）或主要易化子超家族（MFS）转运蛋白的酿酒酵母菌株对米卡芬净和卡泊芬净的敏感性。高表达来自白色念珠菌ABC转运蛋白或MFS转运蛋白单个等位基因的酵母菌株，对氟康唑、伊曲康唑和伏立康唑等唑类药物呈现出预期的耐药谱。如先前报道，在琼脂平板药敏试验中，高表达CDR2的菌株对卡泊芬净的敏感性略有降低，但与高表达CDR1的菌株或缺失7个ABC转运蛋白的亲本菌株相比，对米卡芬净的敏感性增加。在这些试验中，高表达CDR1的菌株对米卡芬净的敏感性略有降低。一株相对于其唑类敏感的同基因祖细胞过表达Cdr1p和Cdr2p的白色念珠菌临床分离株，在琼脂平板药敏试验中获得了对唑类药物的耐药性，对卡泊芬净的敏感性降低，对米卡芬净的敏感性略有增加。在液体微量稀释药敏试验中，所有菌株对米卡芬净或卡泊芬净均未显示出显著耐药性。在琼脂糖扩散试验中，米卡芬净和卡泊芬净的抗真菌活性相似，尽管卡泊芬净抑菌圈的形状和大小受培养基成分影响。因此，米卡芬净和卡泊芬净效力的评估依赖于检测方法；在琼脂平板药敏试验中观察到的差异发生在棘白菌素浓度的狭窄范围内，且无临床意义。
