In vitro Antibiofilm Activity of Eucarobustol E against Candida albicans [PublishAheadOfPrint]

Formyl-phloroglucinol meroterpenoids (FPMs) are an important type of natural products with various bioactivities. Our antifungal susceptibility assay showed that one of the Eucalyptus robusta derived FPMs-Eucarobustol E (EE) exerted strong inhibitory effect against Candida albicans biofilms at a concentration of 16 μg/ml. EE was found to block the yeast-to-hypha transition and reduce the cellular surface hydrophobicity of the biofilm cells. RNA sequencing and real time reverse-transcription PCR analysis showed that exposure to 16 μg/ml of EE resulted in marked reduction of expressions of genes involved in hyphal growth (EFG1, CPH1, TEC1, EED1, UME6, and HGC1) and cell surface proteins (ALS3, HWP1, and SAP5). Interestingly, in response to EE, genes involved in ergosterol biosynthesis were down-regulated while farnesol encoding gene (DPP3) was up-regulated, which were in agreement with the quantification of ergosterol and farnesol. Combining with the obvious elevation of negative regulator genes (TUP1, NRG1), we speculated that EE's inhibitions on carbon flow to ergosterol triggered the negative regulation mechanisms of hyphal growth, and eventually led to biofilm inhibition.

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