Li Xiuyun, Yu Cuixiang, Huang Xin, Sun Shujuan
School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong Province, People's Republic of China.
Respiration Medicine, Qianfoshan Hospital Affiliated to Shandong University, Jinan, Shandong Province, People's Republic of China.
PLoS One. 2016 Dec 22;11(12):e0168936. doi: 10.1371/journal.pone.0168936. eCollection 2016.
Candida albicans is an important opportunistic pathogen, causing both superficial mucosal infections and life-threatening systemic diseases in the clinic. The emergence of drug resistance in Candida albicans has become a noteworthy phenomenon due to the extensive use of antifungal agents and the development of biofilms. This study showed that budesonide potentiates the antifungal effect of fluconazole against fluconazole-resistant Candida albicans strains both in vitro and in vivo. In addition, our results demonstrated, for the first time, that the combination of fluconazole and budesonide can reverse the resistance of Candida albicans by inhibiting the function of drug transporters, reducing the formation of biofilms, promoting apoptosis and inhibiting the activity of extracellular phospholipases. This is the first study implicating the effects and mechanisms of budesonide against Candida albicans alone or in combination with fluconazole, which may ultimately lead to the identification of new potential antifungal targets.
白色念珠菌是一种重要的机会致病菌,在临床上可引起浅表黏膜感染和危及生命的全身性疾病。由于抗真菌药物的广泛使用和生物膜的形成,白色念珠菌耐药性的出现已成为一个值得关注的现象。本研究表明,布地奈德在体外和体内均能增强氟康唑对氟康唑耐药白色念珠菌菌株的抗真菌作用。此外,我们的结果首次证明,氟康唑和布地奈德联合使用可通过抑制药物转运蛋白的功能、减少生物膜的形成、促进细胞凋亡和抑制细胞外磷脂酶的活性来逆转白色念珠菌的耐药性。这是第一项研究布地奈德单独或与氟康唑联合使用对白色念珠菌的作用及机制的研究,这最终可能会导致发现新的潜在抗真菌靶点。