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

View Article: PubMed Central - PubMed

ABSTRACT

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

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The effect of ABH on the (A) uptake and (B) efflux of Rh6G in resistant C. albicans. The uptake and efflux of Rh6G in the absence and presence of ABH (128 μg/mL) were determined by a flow cytometer. Ten thousand events were counted for each sample at specific time intervals. MFIs represent the intracellular Rh6G in C. albicans. GraphPad Prism 6 software was used to analyze the data. The experiments were performed three times on different days.
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Figure 4: The effect of ABH on the (A) uptake and (B) efflux of Rh6G in resistant C. albicans. The uptake and efflux of Rh6G in the absence and presence of ABH (128 μg/mL) were determined by a flow cytometer. Ten thousand events were counted for each sample at specific time intervals. MFIs represent the intracellular Rh6G in C. albicans. GraphPad Prism 6 software was used to analyze the data. The experiments were performed three times on different days.

Mentions: Both Rh6G and FLC are substrates of drug transporters in C. albicans. Rh6G was used as the alternate for FLC in the present study. We measured the uptake and efflux of Rh6G in resistant C. albicans in the absence and presence of ABH. Intracellular Rh6G uptake in the ABH-treated group increased over time, and that in the ABH group increased faster than that in the control group (Figure 4A). Cells treated with ABH pumped out lower concentrations of Rh6G than cells without drug treatment. This finding was evident by the sharp drop in the measured intracellular concentrations of Rh6G in the ABH-treated group (Figure 4B). Our results revealed that ABH can increase the uptake and decrease the efflux of rhodamine 6G.


Ambroxol Hydrochloride Combined with Fluconazole Reverses the Resistance of Candida albicans to Fluconazole
The effect of ABH on the (A) uptake and (B) efflux of Rh6G in resistant C. albicans. The uptake and efflux of Rh6G in the absence and presence of ABH (128 μg/mL) were determined by a flow cytometer. Ten thousand events were counted for each sample at specific time intervals. MFIs represent the intracellular Rh6G in C. albicans. GraphPad Prism 6 software was used to analyze the data. The experiments were performed three times on different days.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5383865&req=5

Figure 4: The effect of ABH on the (A) uptake and (B) efflux of Rh6G in resistant C. albicans. The uptake and efflux of Rh6G in the absence and presence of ABH (128 μg/mL) were determined by a flow cytometer. Ten thousand events were counted for each sample at specific time intervals. MFIs represent the intracellular Rh6G in C. albicans. GraphPad Prism 6 software was used to analyze the data. The experiments were performed three times on different days.
Mentions: Both Rh6G and FLC are substrates of drug transporters in C. albicans. Rh6G was used as the alternate for FLC in the present study. We measured the uptake and efflux of Rh6G in resistant C. albicans in the absence and presence of ABH. Intracellular Rh6G uptake in the ABH-treated group increased over time, and that in the ABH group increased faster than that in the control group (Figure 4A). Cells treated with ABH pumped out lower concentrations of Rh6G than cells without drug treatment. This finding was evident by the sharp drop in the measured intracellular concentrations of Rh6G in the ABH-treated group (Figure 4B). Our results revealed that ABH can increase the uptake and decrease the efflux of rhodamine 6G.

View Article: PubMed Central - PubMed

ABSTRACT

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

No MeSH data available.


Related in: MedlinePlus