摘要
侵袭性真菌感染严重威胁人类生命健康.白念珠菌是临床侵袭性真菌感染中较为常见的菌种之一.耐药性的产生和生物被膜的形成是其临床治疗失败的主要原因.因此,亟需开发抗耐药菌和生物被膜的新型药物.课题组通过药敏筛选实验发现化合物GSK2334470(J1)单用时对耐药白念珠菌表现一定的抑制活性(MIC值范围为32~>128μg/mL),且在较高浓度时(64~256μg/mL)能明显抑制生物被膜的形成及损伤成熟生物被膜.进一步,通过棋盘式微量液基稀释法、生长实验、存活实验、纸片扩散实验、生物被膜实验等证实J1与氟康唑合用后对耐药白念珠菌和热带念珠菌均表现较好的协同抗菌作用,它们能协同抑制耐药白念珠菌的生长以及生物被膜的形成.初步的机制研究发现J1能增加耐药白念珠菌的细胞壁厚度,并且还能抑制其药物的外排.因此,进一步对化合物J1深入研究,有望发现新型抗耐药真菌先导化合物或候选药物.
Invasive fungal infections are a serious threat to human life and health.Candida albicans is one of the more prevalent species of clinically invasive fungal infections.The major causes of unsuccessful clinical treatment are the emergence of drug resistance and biofilm formation.Therefore,there is an urgent need to develop novel drugs against drug-resistant fungi and biofilms.The team discovered that GSK2334470(J1),when used alone,had inhibitory effect against drug-resistant Candida albicans(MIC values ranged from 32 to>128μg/mL),and that at higher concentrations(64~256μg/mL),it significantly inhibited biofilm formation and damaged mature biofilms.Furthermore,the synergistic antifungal effects of J1 in combination with fluconazole(FLC)against drug-resistant Candida albicans and Candida tropicalis were confirmed by checkerboard microdilution method,growth assay,survival assay,paper diffusion assay,and biofilm assay.J1 and FLC were also found to synergistically inhibit the growth and biofilm formation of drug-resistant Candida albicans.Preliminary mechanistic studies revealed that J1 could increase the cell wall thickness of drug-resistant[JP2]Candida albicans and also inhibit its drug efflux.Therefore,further studies on compound J1 are expected to identify novel lead compounds or drug candidates against drug-resistant fungi.
作者
刘伟
张秀秀
韩研春
石俊义
姜婉藤
何志强
代彬
李雅楠
王胜正
LIU Wei;ZHANG Xiu-xiu;HAN Yan-chun;SHI Jun-yi;JIANG Wan-teng;HE Zhi-qiang;DAI Bin;LI Ya-nan;WANG Sheng-zheng(School of Food Science and Engineering(School of Biological and Pharmaceutical Science),Shaanxi University of Science&Technology,Xi′an 710021,China;School of Pharmacy,Fourth Military Medical University,Xi′an 710032,China)
出处
《陕西科技大学学报》
北大核心
2024年第2期72-78,86,共8页
Journal of Shaanxi University of Science & Technology
基金
陕西省科技厅自然科学基金项目(2022JM-498)
陕西省大学生创新创业训练计划项目(S202110708084)
陕西科技大学博士科研启动基金项目(2016BJ-52)。
