Candida albicans has the ability to switch reversibly between budding yeast, filamentous, pseudohypha, and hyphal forms, a process in which the transcription factor Flo8 plays an important role. This ability is important for the virulence and pathogenicity of C. albicans. To determine whether Flo8 plays a role in the regulation of drug sensitivity, we constructed a FLO8 null mutant flo8/flo8 from the parental strain SN152 and a Flo8-overexpressing strain, flo8/flo8::FLO8. The susceptibility of the isolates to antifungal agents was then evaluated using the agar dilution and broth microdilution methods. Expression of drug resistance-related genes by the isolates was investigated by real-time PCR. The flo8/flo8 mutation isolates exhibited increased resistance to fluconazole, voriconazole, and itraconazole compared with the wild-type and drug sensitivity was restored by FLO8 overexpression (flo8/flo8∷FLO8). Of seven drug resistance-related genes, the FLO8 null mutation resulted in increased CDR1 and CDR2 expression (1.60-fold and 5.27-fold, respectively) compared with SN152, while FLO8 overexpression resulted in decreased CDR1 expression (0.63-fold). These results suggest that Flo8 is involved in the susceptibility of C. albicans to antifungal azoles, with FLO8 deletion leading to constitutive overexpression of CDR1 and CDR2 and resistance to antifungal azoles.

中文翻译：

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通过上调白色念珠菌中的CDR1和CDR2，FLO8缺失导致唑类耐药。

白色念珠菌具有在发芽酵母，丝状，假菌丝和菌丝形式之间可逆切换的能力，在该过程中转录因子Flo8起着重要作用。该能力对于白色念珠菌的致病性和致病性很重要。为了确定Flo8是否在药物敏感性的调节中起作用，我们从亲本菌株SN152和过表达Flo8的菌株flo8 / flo8 :: FLO8构建了FLO8无效突变体flo8 / flo8。然后使用琼脂稀释法和肉汤微量稀释法评估分离株对抗真菌剂的敏感性。通过实时PCR研究分离物与药物抗性相关基因的表达。flo8 / flo8突变菌株对氟康唑，伏立康唑，FLO8过表达（flo8 /flo8∷FLO8）恢复了伊曲康唑的野生型和药物敏感性。与SN152相比，在七个与药物抗性相关的基因中，FLO8无效突变导致CDR1和CDR2表达增加（分别为1.60倍和5.27倍），而FLO8过表达导致CDR1表达下降（0.63倍）。这些结果表明，Flo8参与白色念珠菌对抗真菌唑的敏感性，FLO8缺失导致CDR1和CDR2组成型过表达以及对抗真菌唑的抗性。而FLO8过表达导致CDR1表达下降（0.63倍）。这些结果表明，Flo8参与白色念珠菌对抗真菌唑的敏感性，而FLO8缺失导致CDR1和CDR2组成型过表达以及对抗真菌唑的抗性。而FLO8过表达导致CDR1表达下降（0.63倍）。这些结果表明，Flo8参与白色念珠菌对抗真菌唑的敏感性，而FLO8缺失导致CDR1和CDR2组成型过表达以及对抗真菌唑的抗性。