蜚蠊肠道共生戈登氏菌WA12-1-1次级代谢产物喹唑啉-4(3H)-酮抗白色念珠菌活性及作用机制研究  

Mechanistic study of quinazolin-4(3H)-one a secondary metabolite from the Periplaneta americana Symbiont Gordonia sp WA12-1-1 against Candida albicans

作　　者：朱刘冲 黄嘉旋 金小宝[1,2] 汪洁 ZHU Liuchong;HUANG Jiaxuan;JIN Xiaobao;WANG Jie(School of Basic Medical Sciences,Guangdong Pharmaceutical University,Guangzhou 510006,China;Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances,Guangdong Pharmaceutical University,Guangzhou 510006,China;School of Pharmacy,Guangdong Pharmaceutical University,Guangzhou 510006,China)

机构地区：[1]广东药科大学基础医学院,广东广州510006 [2]广东省生物活性药物研究重点实验室,广东广州510006 [3]广东药科大学药学院,广东广州510006

出　　处：《广东药科大学学报》2025年第2期38-47,共10页Journal of Guangdong Pharmaceutical University

基　　金：广东省自然科学基金项目(2020A1515011097);广东省医学科学技术研究基金(A2024478)。

摘　　要：目的探究来源于蜚蠊肠道戈登氏菌WA12-1-1次级代谢产物喹唑啉-4(3H)-酮[quinezolin-4(3H)-one]对白色念珠菌的作用和机制。方法微量稀释法测定喹唑啉-4(3H)-酮对白色念珠菌的最小抑菌浓度(MIC);ELISA法检测β-1,3-D-葡聚糖合酶(β-1,3-D-GS)、几丁质合成酶(CS)、角鲨烯环氧酶(SQLE)和14α-去甲基化酶(CYP51)活性;酶标仪测定细胞内核酸释放量;DCFH-DA探针和JC荧光探针测白色念珠菌胞线粒体膜电位;碘化丙啶(PI)染色法检测化合物对细胞膜通透性的影响;HPLC法检测胞内麦角甾醇含量。结果Quinezolin-4(3H)-on对白色念珠菌的最小抑菌浓度为64μg/mL,能抑制念珠菌假菌丝的形成;Quinezolin-4(3H)-on降低细胞内SQLE和CYP51酶活性,与对照组比较差异有统计学意义(P<0.05或P<0.01);Quinezolin-4(3H)-one处理后念珠菌细胞核酸释放量增加,胞内麦角甾醇含量降低,PI染色细胞数量增多;线粒体膜电位降低,与对照组相比具有统计学意义。结论从戈登氏菌WA12-1-1中分离得到的quinezolin-4(3H)-one能抑制白色念珠菌的生长,其主要作用机制是破坏白色念珠菌细胞膜结构、抑制菌丝生成以及影响线粒体功能。Objective To investigate the effect and mechanism of quinezolin-4(3H)-one,a secondary metabolite derived from Gordonia sp.WA12-1-1 colonizing the intestine of Periplaneta americana,on Candida albicans.Methods The minimum inhibitory concentration(MIC)of Quinezolin-4(3H)-one against C.albicans was determined using the microdilution method.An enzyme-linked immunosorbent assay(ELISA)was used to detect the activities of β-1,3-D-glucan synthase(β-1,3-D-GS),chitin synthase(CS),squalene epoxidase(SQLE),and 14α-demethylase(CYP51).The intracellular nucleic acid release was measured via an ELISA reader.The DCFH-DA and JC-1 fluorescence probes were utilized to assess mitochondrial membrane potential in C.albicans.Propidium iodide(PI)staining was employed to examine the compound's impact on cell membrane permeability,and HPLC was used to measure intracellular ergosterol content.Results The quinezolin-4(3H)-one inhibited hyphal formation in C.albicans with MIC of 64μg/mL.Quinezolin-4(3H)-one significantly reduced intracellular SQLE and CYP51 enzyme activities compared to the control group.Additionally,C.albicans cells treated with quinezolin-4(3H)-one exhibited increased nucleic acid release,reduced intracellular ergosterol content,and a higher number of PI-stained cells.The mitochondrial membrane potential was also significantly lowered compared to the control group.Conclusion Quinezolin-4(3H)-one,isolated from Gordonia WA12-1-1,inhibits the growth of C.albicans.Its mechanism primarily involves disruption of the C.albicans cell membrane structure,inhibition of hyphal formation,and reduction of mitochondrial membrane potential.

关 键 词：白色念珠菌 喹唑啉-4(3H)-酮 抗真菌机制 

分 类 号：R392.1[医药卫生—免疫学]