Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China.
College of Life Sciences, Sichuan Agricultural University, Chengdu 611130, China.
Int J Mol Sci. 2023 May 16;24(10):8855. doi: 10.3390/ijms24108855.
is an opportunistic pathogen that can cause severe or even fatal infections in patients with low immune function. plays different roles in different fungi and is also related to fungal drug resistance. However, the mechanism underlying its drug resistance to azoles has not yet been reported in . Therefore, we investigated the drug resistance of () by constructing overexpressing mutant strains (TaPLA2). TaPLA2 was generated by homologous recombination of the recombinant vector pEGFP-N1-TaPLA2, induced by the CMV promoter, with . The structure of the protein was found to be typical of sPLA2, and it belongs to the phospholipase A2_3 superfamily. TaPLA2 enhanced antifungal drug resistance by upregulating the expression of effector genes and increasing the number of arthrospores to promote biofilm formation. TaPLA2 was highly sensitive to sodium dodecyl sulfate and Congo red, indicating impaired cell wall integrity due to downregulation of chitin synthesis or degradation genes, which can indirectly affect fungal resistance. In conclusion, overexpression enhanced the resistance to azoles of by enhancing drug efflux and biofilm formation and upregulating HOG-MAPK pathway genes; therefore, it has promising research prospects.
是一种机会致病菌，可导致免疫功能低下的患者发生严重甚至致命的感染。 在不同真菌中发挥不同作用，与真菌耐药性也有关。然而，在 中，其唑类药物耐药性的机制尚未报道。因此，我们通过构建过表达突变株（TaPLA2）来研究 （）的耐药性。TaPLA2 通过重组载体 pEGFP-N1-TaPLA2 与 的同源重组，由 CMV 启动子诱导产生。发现该蛋白的结构为典型的 sPLA2，属于磷脂酶 A2_3 超家族。TaPLA2 通过上调效应基因的表达和增加分生孢子的数量来促进生物膜形成，从而增强抗真菌药物的耐药性。TaPLA2 对十二烷基硫酸钠和刚果红高度敏感，表明由于几丁质合成或降解基因下调导致细胞壁完整性受损，这可能间接影响真菌耐药性。总之，过表达 TaPLA2 通过增强药物外排和生物膜形成以及上调 HOG-MAPK 通路基因来增强对唑类药物的耐药性；因此，它具有广阔的研究前景。
