PUB - Publikationen an der Universität Bielefeld

AIM: The present study aimed to investigate a novel antifungal compound produced by Streptomyces blastmyceticus S108 strain. Its effectiveness against clinical isolates of Candida species and its synergistic effect with conventional antifungal drugs were assessed and its molecular mechanism of action was further studied against C. albicans.; METHODS AND RESULTS: A newly isolated strain from Tunisian soil, Streptomyces blastmyceticus S108, showed significant antifungal activity against Candida species by well diffusion method. The butanolic extract of S108 strain supernatant exhibited the best anti-Candida activity with a minimal inhibitory concentration (MIC) value of 250 mug mL-1, determined by the microdilution method. The bio-guided purification steps of the butanolic extract were performed by chromatographic techniques. Among the fractions obtained, F13 demonstrated the highest level of activity, displaying a MIC of 31.25 mug mL-1. Gas Chromatography-Mass Spectrometry (GC-MS) and Electrospray Ionisation Mass Spectrometry (ESI-MS) analyses of this fraction (F13) revealed the glycolipidic nature of the active molecule with a molecular weight of 685.6 m/z. This antifungal metabolite remained stable to physicochemical changes and did not show hemolytic activity even at 4 MIC corresponding to 125 g mL-1 towards human erythrocytes. Besides, the glycolipid compound was combined with 5-flucytosine and showed a high synergistic effect with a FICI value 0.14 against C. albicans ATCC 10231. This combination resulted in a decrease of MIC values of 5-flucytosine and the glycolipid-like compound by 8 and 64-fold, respectively. The examination of gene expression in treated Candida albicans cells by qPCR revealed that the active compound tested alone or in combination with 5-flucytosine blocks the ergosterol biosynthesis pathway by down regulating the expression of ERG1, ERG3, ERG5, ERG11 and ERG25 genes.; CONCLUSION AND IMPACT OF THE STUDY: The new glycolipid like compound, produced by Streptomyces S108 isolate, could be a promising drug for medical use against pathogenic Candida isolates. © The Author(s) 2023. Published by Oxford University Press on behalf of Applied Microbiology International.