Matsumoto Yasuhiko, Nagamachi Tae, Yoshikawa Asami, Yamada Tsuyoshi, Sugita Takashi
Department of Microbiology, Meiji Pharmaceutical University, 2-522-1, Noshio, Kiyose, Tokyo, 204-8588, Japan.
Teikyo University Institute of Medical Mycology, 359 Otsuka, Hachioji, Tokyo, 192-0395, Japan.
AMB Express. 2022 Jul 14;12(1):91. doi: 10.1186/s13568-022-01431-9.
Trichosporon asahii is a pathogenic fungus that causes deep-seated fungal infections in immunocompromised patients. Established methods for generating gene-deficient T. asahii mutants exist, but the frequency of obtaining transformants by electroporation remains low. In the present study, we optimized the conditions for gene transfer by electroporation using a ku70 gene-deficient mutant with high recombination efficiency. Introducing a DNA fragment by electroporation into T. asahii cells on Sabouraud dextrose agar to generate a cnb1 gene-deficient mutant and incubating for 1 day led to the growth of approximately 100 transformants. When the incubation period was extended to 2 days or 5 days, however, only 2 or no transformants, respectively, were grown. The highest number of transformants was grown by electroporation when a square wave at 1.8 kV (9 kV/cm) was applied for 5 ms. In addition, the number of transformants increased with an increase in the length of the homologous region, and transformants did not grow when the homologous region was less than 500 base pairs. A DNA fragment was produced for deletion of the cnb1 gene by joint PCR, and the cnb1 gene-deficient mutant was obtained by introducing the DNA fragment by electroporation. These results indicate that DNA fragments produced by joint PCR can be used to generate gene-deficient mutants of T. asahii through gene transfer by electroporation.
白吉利丝孢酵母是一种致病性真菌,可在免疫功能低下的患者中引起深部真菌感染。虽然存在生成白吉利丝孢酵母基因缺陷突变体的既定方法,但通过电穿孔获得转化体的频率仍然很低。在本研究中,我们使用重组效率高的ku70基因缺陷突变体优化了电穿孔基因转移的条件。通过电穿孔将DNA片段导入Sabouraud葡萄糖琼脂上的白吉利丝孢酵母细胞中以生成cnb1基因缺陷突变体,并孵育1天,可产生约100个转化体。然而,当孵育期延长至2天或5天时,分别仅生长2个或没有转化体。当施加1.8 kV(9 kV/cm)的方波5 ms时,通过电穿孔生长的转化体数量最多。此外,转化体的数量随着同源区域长度的增加而增加,当同源区域小于500个碱基对时,转化体不生长。通过联合PCR产生用于缺失cnb1基因的DNA片段,并通过电穿孔引入该DNA片段获得cnb1基因缺陷突变体。这些结果表明,联合PCR产生的DNA片段可用于通过电穿孔基因转移产生白吉利丝孢酵母的基因缺陷突变体。