Synergistic Anti-Candida Activity of Bengazole A in the Presence of Bengamide A

Abstract

Bengazoles A–G from the marine sponge Jaspis sp. exhibit potent in vitro antifungal activity against Candida spp. and other pathogenic fungi. The mechanism of action (MOA) of bengazole A was explored in Candida albicans 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 Jaspis sp. The MOA of bengazole A was further explored by monitoring the sterol composition of C. albicans in the presence of sub-lethal concentrations of bengazole A. The GCMS of solvent extracts prepared from liquid cultures of C. albicans 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 C. albicans 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.

Antifungal activity of Streptomyces spp. against Pyrenophora tritici-repentis the causal agent of tan spot in wheat

“…Bengamide also appeared in LC/MS analyses of the study from Zeyad et al (2022), previously quoted, but the authors did not present any observations about this compound. However, studies from Jamison et al (2019) observed the potent antifungal activity of the bengamide associated with bengazole against Candida. The action mechanism was methionine aminopeptidases (MetAPs) inhibition.…”

The Development of the Bengamides as New Antibiotics against Drug-Resistant Bacteria

“…Conversely, the bengazoles, which are the second most common secondary metabolites found in Jaspis species (Figure 5), stand out for their antifungal activity against Candida albicans [50,51], displaying comparable values of inhibition with amphotericin B and with a similar mode of action [52]. In a recent study conducted by Molinski et al [53], it was found a synergistic activity of a mixture of bengamide A (1) and bengazoles A-G (59a-g). In fact, it was observed that while pure bengazoles presented a MIC value of 1 µM against C. albicans at 0.5 µg/disk, inducing a zone of inhibition of 9-10 mm, a sample containing a mixture of bengazoles and bengamides produced a larger inhibition zone of 40 mm.…”