Li Ying, Chang Wenqiang, Zhang Ming, Li Xiaobin, Jiao Yang, Lou Hongxiang
Department of Natural Product Chemistry, Key Lab of Chemical Biology of Ministry of Education, Shandong University, No. 44 West Wenhua Road, Jinan City, Shandong Province 250012, China.
Department of Natural Product Chemistry, Key Lab of Chemical Biology of Ministry of Education, Shandong University, No. 44 West Wenhua Road, Jinan City, Shandong Province 250012, China
FEMS Yeast Res. 2015 Mar;15(2). doi: 10.1093/femsyr/fov001. Epub 2015 Mar 8.
The emergence of drug resistance and limitation of antifungal agents bring enormous challenges to the management of Candida infection. Combination therapy is a useful way to treat the fungal infection, especially for those difficult-to-treat infections. In this research, we investigated the interaction effects between diorcinol D (DD), an antifungal active natural product from lichen endophytic fungus and fluconazole (FLC) against planktonic cells and mature biofilms of Candida albicans in vitro by checkerboard microdilution and time-killing tests. Both fractional inhibitory concentration index model and ΔE model revealed a synergistic antifungal action between DD and FLC against all five azole-resistant isolates and synergistic or indifferent effects for other five azole-sensitive isolates. In addition, the synergies were obtained from eradicating C. albicans mature biofilms tests using two wild-type strains (SC5314 and YEM30), an azole-resistant isolate 28I and an azole-sensitive isolate 18B. The time-killing tests also showed synergistic fungicidal action between DD and FLC. Mechanism test revealed that DD inhibited the activity of efflux pump and retarded the biosynthesis of ergosterol, which probably contributed to the synergetic action as well as the reversing activity of drug resistance.
耐药性的出现以及抗真菌药物的局限性给念珠菌感染的治疗带来了巨大挑战。联合治疗是治疗真菌感染的一种有效方法，尤其是对于那些难治性感染。在本研究中，我们通过棋盘微量稀释法和时间杀菌试验，研究了地衣内生真菌的抗真菌活性天然产物二羟基萘酚D（DD）与氟康唑（FLC）对白色念珠菌浮游细胞和成熟生物膜的体外相互作用。最低抑菌浓度分数指数模型和ΔE模型均显示，DD与FLC对所有5株耐唑类菌株均有协同抗真菌作用，对其他5株唑类敏感菌株有协同或无明显作用。此外，使用两株野生型菌株（SC5314和YEM30）、一株耐唑类菌株28I和一株唑类敏感菌株18B进行的白色念珠菌成熟生物膜清除试验也获得了协同作用。时间杀菌试验也显示了DD与FLC之间的协同杀菌作用。机制试验表明，DD抑制了外排泵的活性，延缓了麦角甾醇的生物合成，这可能有助于协同作用以及耐药性的逆转。
