AUTHOR=Li Xiuyun , Wu Xuexin , Gao Yan , Hao Lina 

TITLE=Synergistic Effects and Mechanisms of Combined Treatment With Harmine Hydrochloride and Azoles for Resistant Candida albicans

JOURNAL=Frontiers in Microbiology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2019.02295

DOI=10.3389/fmicb.2019.02295

ISSN=1664-302X

ABSTRACT=<p>Several studies have demonstrated the significant antiviral, antimicrobial, antiplasmodial, antioxidative, antifungal, antimutagenic, and antitumor properties of harmine hydrochloride (HMH). The main objective of the present study was to investigate the antifungal effects and underlying mechanisms of HMH when combined with azoles to determine whether such combinations act in a synergistic manner. As a result, we found that HMH exhibits synergistic antifungal effects in combination with azoles against resistant <italic>Candida albicans</italic> (<italic>C. albicans</italic>) planktonic cells, as well as resistant <italic>C. albicans</italic> biofilm in the early stage. Antifungal potential of HMH with fluconazole was also explored <italic>in vivo</italic> using an invertebrate model. Our results suggest that HMH combined with azoles is synergistic against resistant <italic>C. albicans in vitro</italic> and <italic>in vivo</italic>. No synergy is seen with azole sensitive <italic>C. albicans</italic> strains nor with other <italic>Candida</italic> species. Such synergistic mechanisms on resistance <italic>C. albicans</italic> are involved in increasing intracellular azoles, inhibiting hyphal growth, disturbing cytosolic calcium concentration, and inducing apoptosis of resistant <italic>C. albicans</italic> cells.</p>