Abstract
Here we describe the antimicrobial potential of secondary metabolites, fulvic acid (F.A.) and anhydrofulvic acid (AFA), produced by RDE147, an endophyte of Rosa damascena Mill. The endophyte was identified as Cercospora piaropi by ITS and β-tubulin–based phylogenetic analyses, while chemoprofiling of the endophyte by column chromatography and spectroscopy yielded two pure compounds, F.A. and AFA. The compounds demonstrated different antimicrobial profiles, with AFA suppressing the growth of C. albicans at 7.3 µg ml−1 IC50. Further studies revealed that AFA strongly restricted the biofilm production and hyphae formation in C. albicans by down-regulating several biofilm and morphogenesis-related genes. The time-kill assays confirmed the fungicidal activity of AFA against C. albicans, killing 83.6% of the pathogen cells in 24 h at the MIC concentration, and the post-antibiotic effect (PAE) experiments established the suppression of C. albicans growth for extended time periods. The compound acted synergistically with amphotericin B and nystatin and reduced ergosterol biosynthesis by the pathogen, confirmed by ergosterol estimation and comparative expression profiling of selected genes and molecular docking of AFA with C. albicans squalene epoxidase. AFA also suppressed the expression of several other virulence genes of the fungal pathogen. The study determines the anti-C. albicans potential of AFA and its impact on the biology of the pathogen. It also indicates that Cercospora species may yield potential bioactive molecules, especially fulvic acid derivatives. However, it is imperative to conduct in vivo studies to explore this molecule’s therapeutic potential further.
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Data Availability
The pure culture (Voucher no. MRCJ–1029) was deposited in the institute’s in-house microbial repository (WDCM 1117). The ITS and β-tubulin gene sequences were deposited with GenBank accession numbers OK335281 and OL862418, respectively.
Code Availability
Not applicable.
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Acknowledgements
AB is supported by a Senior Research Fellowship of the University Grant Commission, New Delhi. T.A. and S.F. obtain fellowships from the Department of Science and Technology, New Delhi. Approval of the institutional IPR committee was obtained with the manuscript no. CSIR-IIIM/IPR/00386.
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The project MLP1008 is supported by the Council of Scientific and Industrial Research (CSIR), New Delhi.
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Bashir, A., Ahmad, T., Farooq, S. et al. A Secondary Metabolite of Cercospora sp., Associated with Rosa damascena Mill., Inhibits Proliferation, Biofilm Production, Ergosterol Synthesis and Other Virulence Factors in Candida albicans. Microb Ecol 85, 1276–1287 (2023). https://doi.org/10.1007/s00248-022-02003-x
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DOI: https://doi.org/10.1007/s00248-022-02003-x