Journal
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Volume 61, Issue 8, Pages -Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.02707-16
Keywords
Candida albicans; eucarobustol E; antibiofilm; formyl-phloroglucinol meroterpenoids; negative regulation; natural antimicrobial products
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Funding
- National Natural Science Foundation of China [81503218]
- Program for Changjiang Scholars and the Innovative Research Team in University [IRT_15R63]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
- Fundamental Research Funds for the Central Universities [2016ZZD010]
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Formyl-phloroglucinol meroterpenoids (FPMs) are important types of natural products with various bioactivities. Our antifungal susceptibility assay showed that one of the Eucalyptus robusta-derived FPMs, eucarobustol E (EE), exerted a strong inhibitory effect against Candida albicans biofilms at a concentration of 16 mu g/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 mu g/ml of EE resulted in marked reductions in the levels of expressions of genes involved in hyphal growth (EFG1, CPH1, TEC1, EED1, UME6, and HGC1) and cell surface protein genes (ALS3, HWP1, and SAP5). Interestingly, in response to EE, genes involved in ergosterol biosynthesis were downregulated, while the farnesol-encoding gene (DPP3) was upregulated, and these findings were in agreement with those from the quantification of ergosterol and farnesol. Combined with the obvious elevation of negative regulator genes (TUP1, NRG1), we speculated that EE's inhibition of carbon flow to ergosterol triggered the mechanisms of the negative regulation of hyphal growth and eventually led to biofilm inhibition.
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