Journal
JOURNAL OF FUNGI
Volume 8, Issue 2, Pages -Publisher
MDPI
DOI: 10.3390/jof8020121
Keywords
Mucorales; antifungal combination; amphotericin B
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This study evaluated the effect of the combination of amphotericin B (AmB) and various non-ionic surfactants on the activity of AmB against Mucorales, the toxicity on eukaryotic cells, and the modification of AmB aggregation states. The results showed that PEG15HS increased the efficacy of AmB against Mucorales without increasing its toxicity.
The aim of this study was to evaluate the effect of the combination of amphotericin B (AmB) and various non-ionic surfactants on the anti-Mucorales activity of AmB, the toxicity of the combination on eukaryotic cells and the modification of AmB aggregation states. Checkerboards were performed on five genera of Mucorales (12 strains) using several combinations of different surfactants and AmB. These data were analyzed by an E-max model. The effect of surfactants on the cytotoxic activity of AmB was then evaluated for red blood cells and two eukaryotic cell lines by absorbance and propidium iodide internalization. Finally, the effect of polyethylene glycol (15)-hydroxystearate (PEG15HS) on the aggregation states of AmB was evaluated by UV-visible spectrometry. PEG15HS increased the efficacy of AmB on four of the five Mucorales genera, and MICs of AmB were decreased up to 68-fold for L. ramosa. PEG15HS was the only surfactant to not increase the cytotoxic activity of AmB. Finally, the analysis of AmB aggregation states showed that the increased efficacy of AmB and the absence of toxicity are related to an increase in monomeric and polyaggregated forms of AmB at the detriment of the dimeric form. In conclusion, PEG15HS increases the in vitro efficacy of AmB against Mucorales at low concentration, without increasing its toxicity; this combination could therefore be evaluated in the treatment of mucormycosis.
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