Synergistic Anti-<em>Candida</em> Activity of Bengazole A in the Presence of Bengamide A
Bengazoles A–G from the marine sponge <i>Jaspis</i> sp. exhibit potent in vitro antifungal activity against <i>Candida</i> spp. and other pathogenic fungi. The mechanism of action (MOA) of bengazole A was explored in <i>Candida albicans</i> under both liquid cultu...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2019-02-01
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| Series: | Marine Drugs |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1660-3397/17/2/102 |
| Summary: | Bengazoles A–G from the marine sponge <i>Jaspis</i> sp. exhibit potent in vitro antifungal activity against <i>Candida</i> spp. and other pathogenic fungi. The mechanism of action (MOA) of bengazole A was explored in <i>Candida albicans</i> under both liquid culture and surface culture on Mueller-Hinton agar. Pronounced dose-dependent synergistic antifungal activity was observed with bengazole A in the presence of bengamide A, which is also a natural product from <i>Jaspis</i> sp. The MOA of bengazole A was further explored by monitoring the sterol composition of <i>C. albicans</i> in the presence of sub-lethal concentrations of bengazole A. The GCMS of solvent extracts prepared from liquid cultures of <i>C. albicans</i> in the presence of clotrimazole―a clinically approved azole antifungal drug that suppresses ergosterol biosynthesis by the inhibition of 14α-demethylase―showed reduced cellular ergosterol content and increased concentrations of lanosterol and 24-methylenedihydrolanosterol (a shunt metabolite of ergosterol biosynthesis). No change in relative sterol composition was observed when <i>C. albicans</i> was cultured with bengazole A. These results eliminate an azole-like MOA for the bengazoles, and suggest that another as-yet unidentified mechanism is operative. |
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| ISSN: | 1660-3397 |