Multiple efflux mechanisms are involved in Candida albicans fluconazole resistance
Multiple efflux mechanisms are involved in Candida albicans fluconazole resistance
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DOI：
10.1128/aac.40.12.2835
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发表时间：
1996-12-01
影响因子：
4.9
通讯作者：
Jenkinson, HF
中科院分区：
文献类型：
--
作者：
Albertson, GD;Niimi, M;Jenkinson, HF
氟康唑敏感的白色念珠菌菌株以约2 pmol/min/10（9）个细胞的速率蓄积[H-3]氟康唑。用叠氮化钠或2-脱氧葡萄糖预处理细胞不影响氟康唑蓄积。在高浓度下，氟康唑蓄积速率达到饱和，不受加入酮康唑的影响，在4 ℃孵育的细胞中没有氟康唑蓄积。一株抗氟康唑的C.在含氟康唑的培养基中生长富集后分离白色念珠菌SGY-243。与SGY-243相比，命名为FR 2的突变株细胞显示出氟康唑积累速率降低，并且对其他唑类抗真菌剂不耐药。氟康唑在C.白念珠菌FR 2和其他唑类耐药菌株B59630、AD和KB在叠氮化钠存在下增加，表明这些菌株中的氟康唑耐药性可能与能量依赖性药物外排有关。抗氟康唑C.白色念珠菌菌株都含有升高量（2至17倍）的mRNA编码Cdr 1，ATP结合盒型转运蛋白。此外，C.白色念珠菌FR 2还含有增加量的编码Ben（r）的mRNA，Ben（r）是一种主要的易化超家族转运蛋白。这些结果表明，氟康唑进入C。氟康唑耐药可能涉及与Ben（r）和/或Cdr 1表达增加相关的能量依赖性药物外排。
Fluconazole-susceptible Candida albicans strains accumulated [H-3]fluconazole at a rate of approximately 2 pmol/min per 10(9) cells. Fluconazole accumulation was not affected by the pretreatment of cells with sodium azide or with 2-deoxyglucose. The rate of fluconazole accumulation became saturated at high fluconazole concentrations and was not affected by the addition of ketoconazole, and there was no fluconazole accumulation in cells incubated at 4 degrees C. A fluconazole-resistant mutant of C. albicans SGY-243 was isolated following growth enrichment in fluconazole-containing medium. Cells of the mutant strain, designated FR2, showed a reduced rate of fluconazole accumulation compared with SGY-243 and were not resistant to other azole antifungal agents. The rates of fluconazole accumulation by C. albicans FR2 and the other azole-resistant strains, B59630, AD, and KB, were increased in the presence of sodium azide, suggesting that fluconazole resistance in these strains may be associated with an energy-dependent drug efflux. Fluconazole-resistant C. albicans strains all contained elevated amounts (2- to 17-fold) of mRNA encoding Cdr1, an ATP-binding cassette-type transporter. In addition, C. albicans FR2 also contained increased amounts of mRNA encoding Ben(r), a major facilitator superfamily transporter. These results suggest that fluconazole enters C. albicans cells by facilitated diffusion and that fluconazole resistance may involve energy-dependent drug efflux associated with increased expression of Ben(r) and/or Cdr1.