Liu Xinning, Li Tao, Wang Decai, Yang Yilei, Sun Wenwen, Liu Jianqiao, Sun Shujuan
Department of Clinical Pharmacy, Taishan Medical University, Taian, China.
Department of Microbial and Biochemical Pharmacy, School of Medicine and Pharmacy, Ocean University of China, Qingdao, China.
Front Microbiol. 2017 Nov 7;8:2101. doi: 10.3389/fmicb.2017.02101. eCollection 2017.
() is one of the important opportunistic fungal pathogens that is closely associated with disseminated or chronic infections. The objective of this study is to evaluate the synergistic antifungal effect of licofelone, which is dual microsomal prostaglandin E2 synthase/lipoxygenase (mPGES-1/LOX) inhibitor in combination with fluconazole against . Here our results showed that licofelone (16 μg/mL) can synergistically work with fluconazole (1 μg/mL) against planktonic cells of fluconazole-resistant The two-drug combination inhibited the biofilm formation over 12 h, and reduced the expression of extracellular phospholipase genes, biofilm-specific genes and RAS/cAMP/PKA pathway related genes. In addition, the two-drug combination inhibited the transition from yeast to hyphal growth form, and decreased the secreted aspartyl proteinase activity, while not affecting the drug efflux pumps activity. model was also used to confirm the antifungal activity of the drug combination . This study first indicates that the combination of fluconazole and licofelone has synergistic effect against resistant and could be a promising therapeutic strategy for the antifungal treatment.
（）是与播散性或慢性感染密切相关的重要机会性真菌病原体之一。本研究的目的是评估双微粒体前列腺素E2合酶/脂氧合酶（mPGES-1/LOX）抑制剂利考非酮与氟康唑联合使用对（）的协同抗真菌作用。我们的结果表明，利考非酮（16μg/mL）可与氟康唑（1μg/mL）协同作用对抗耐氟康唑的浮游细胞。两药联合在12小时内抑制了（）生物膜的形成，并降低了细胞外磷脂酶基因、生物膜特异性基因和RAS/cAMP/PKA途径相关基因的表达。此外，两药联合抑制了从酵母到菌丝生长形式的转变，并降低了分泌天冬氨酸蛋白酶的活性，同时不影响药物外排泵的活性。（）模型也用于证实药物组合的抗真菌活性。本研究首次表明，氟康唑和利考非酮联合使用对耐药（）具有协同作用，可能是一种有前景的抗真菌治疗策略。
