常见致病真菌唑类耐药基因研究进展

Genes associated with azole resistance in common pathogenic fungi： an update

随着唑类抗真菌药物在临床的广泛应用，耐药现象日益突出。真菌耐药基因突变或表达水平的改变是对唑类耐药的主要原因之一，也一直是国内外关注的热点。参与真菌唑类耐药的基因主要涉及影响麦角甾醇合成途径的相关基因，如ERG11、ERG3；药物外排蛋白相关基因，如编码ABC蛋白的CDR基因、编码MFS泵的MDR基因、钙调神经磷酸酶通路的靶基因RTA2基因。然而，一些基因是否介导真菌唑类耐药仍存在争议或证据不足，如白念珠菌的FLU1基因、光滑念珠菌的ERG11基因。不同类型真菌唑类耐药的主导基因也有差异。

With the widespread application of azole antifungal agents in clinical practice, azole resistance has become increasingly prominent. Mutations or expression changes of associated genes are the main cause of azole resistance, and also a research focus at home and abroad. Azole resistance-associated genes mainly include genes involved in the ergosterol synthesis pathway such as ERGll, ERG3, drug efflux protein-related genes such as CDR genes encoding ABC proteins and MDR genes encoding MFS pump, and the calcineurin target gene RTA2. However, there is still a controversy about, or no sufiqeient evidence for, the relationship between azole resistance and some genes, such as the FLU1 gene of Candida albicans and the ERG11 gene of Candida glabrata. Moreover, interstrain differences exist in azole resistance-mediating genes.