A novel diterpenic derivative produced by Streptomyces chrestomyceticus ADP4 is a potent inhibitor of biofilm and virulence factors in Candida albicans and C. auris.

Abstract

Isolation, identification, structural and functional characterization of potent anti-Candida compound with specific antagonistic activities against significant human pathogens, Candida albicans and C. auris. The compound (55B3) was purified from the metabolites produced by Streptomyces chrestomyceticus ADP4 by employing column chromatography. The structure of 55B3 was determined from the analyses of spectral data that included LCMS, nuclear magnetic resonance, FTIR, and UV spectroscopies. It was identified as a novel derivative of diterpenic aromatic acid, 3-(dictyotin-11'-oate-15'α, 19'β-olide)-4-(dictyotin-11'-oate-15″α, 19″β-olide)-protocatechoic acid. The compound displayed potent antifungal and anti-biofilm activities against C. albicans ATCC 10231 (Minimum Inhibitory Concentration, MIC90:14.94±0.17 μgmL-1 and MBIC90: 16.03±1.1 μgmL-1) and against C. auris CBS 12372 (MIC90: 21.75±1.5 μgmL-1 and Minimum Biofilm Inhibitory Concentration, MBIC90: 18.38±1.78 μgmL-1). Further, pronounced inhibition of important virulence attributes of Candida spp., e.g. yeast-to-hyphae transition, secretory aspartyl proteinase and phospholipase B by 55B3 was noted at subinhibitory concentrations. A plausible mechanism of anti-Candida action of the compound appeared to be the inhibition of ergosterol biosynthesis, which was inhibited by 64±3% at the MIC90 value. The non-cytotoxic attribute of the compound was noted in the liver cell line (HepG2 cells). The present work led to the discovery of a novel diterpenic derivative produced by S. chrestomyceticus ADP4. The compound displayed potent anti-Candida activity, particularly against the two most significant human pathogens, C. albicans and C. auris, which underlined its significance as a potential drug candidate for infections involving these pathogens.