AUTHOR=Li Xiuyun , Zhao Yuanhao , Huang Xin , Yu Cuixiang , Yang Yilei , Sun Shujuan 

TITLE=Ambroxol Hydrochloride Combined with Fluconazole Reverses the Resistance of Candida albicans to Fluconazole

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=7

YEAR=2017

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2017.00124

DOI=10.3389/fcimb.2017.00124

ISSN=2235-2988

ABSTRACT=<p>In this study, we found that ambroxol hydrochloride (128 μg/mL) exhibits synergistic antifungal effects in combination with fluconazole (2 μg/mL) against resistant planktonic <italic>Candida albicans</italic> (<italic>C. albicans</italic>) cells. This combination also exhibited synergistic effects against resistant <italic>C. albicans</italic> biofilms in different stages (4, 8, and 12 h) according to the microdilution method. <italic>In vitro</italic> data were further confirmed by the success of this combination in treating <italic>Galleria mellonella</italic> infected by resistant <italic>C. albicans</italic>. With respect to the synergistic mechanism, our result revealed that ambroxol hydrochloride has an effect on the drug transporters of resistant <italic>C. albicans</italic>, increasing the uptake and decreasing the efflux of rhodamine 6G, a fluorescent alternate of fluconazole. This is the first study to investigate the <italic>in vitro</italic> and <italic>in vivo</italic> antifungal effects, as well as the possible synergistic mechanism of ambroxol hydrochloride in combination with fluconazole against resistant <italic>C. albicans</italic>. The results show the potential role for this drug combination as a therapeutic alternative to treat resistant <italic>C. albicans</italic> and provide insights into the development of antifungal targets and new antifungal agents.</p>