Synergistic and drug-resistant reversing effects of diorcinol D combined with fluconazole against Candida albicans.
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.
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.
Ying
Y
Li
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.
Wenqiang
W
Chang
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.
Ming
M
Zhang
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.
Xiaobin
X
Li
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.
Yang
Y
Jiao
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 louhongxiang@sdu.edu.cn.
Hongxiang
H
Lou
D000935:Antifungal Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects* / Q000502:physiology; D025141:Drug Resistance, Fungal / Q000187:drug effects*; D004357:Drug Synergism; D015725:Fluconazole / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D012118:Resorcinols / Q000494:pharmacology*
D000935:Antifungal Agents; D012118:Resorcinols; C005282:orcinol; D015725:Fluconazole
Candida albicans; diorcinol D; drug-resistant reversing; fluconazole; synergism