Abstract
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.
Highlights
Candida albicans (C. albicans) is the leading human fungal pathogen, and the incidence of invasive fungal infections caused by C. albicans is rising, along with an increasing mortality rate [1,2,3]
Biofilms formed on medical devices provide protection from environmental stress for C. albicans and enhance the resistance of C. albicans to antifungal agents by up to 1000-fold greater than that needed for the treatment of its planktonic counterparts [10,11,12]
Our results demonstrated that the combination of FLC and BUD can reverse the resistance of C. albicans by inhibiting the function of drug transporters, reducing the formation of biofilms, promoting apoptosis and inhibiting the activity of extracellular phospholipases
Summary
Candida albicans (C. albicans) is the leading human fungal pathogen, and the incidence of invasive fungal infections caused by C. albicans is rising, along with an increasing mortality rate [1,2,3]. The excessive and indiscriminate use of FLC in the clinic has led to the emergence of drug resistance in C. albicans [7,8,9]. Biofilms formed on medical devices provide protection from environmental stress for C. albicans and enhance the resistance of C. albicans to antifungal agents by up to 1000-fold greater than that needed for the treatment of its planktonic counterparts [10,11,12]. It is necessary to develop new antifungal strategies that can eliminate the phenomenon of drug resistance in C. albicans. The discovery of new antifungal agents is a complicated and long-term process [13, 14]. To develop new approaches for the treatment of invasive fungal infections, combination therapy may be PLOS ONE | DOI:10.1371/journal.pone.0168936. To develop new approaches for the treatment of invasive fungal infections, combination therapy may be PLOS ONE | DOI:10.1371/journal.pone.0168936 December 22, 2016
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