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Metabolites from Marine-Derived Fungi as Potential Antimicrobial Adjuvants.

ABSTRACT: Marine-derived fungi constitute an interesting source of bioactive compounds, several of which exhibit antibacterial activity. These acquire special importance, considering that antimicrobial resistance is becoming more widespread. The overexpression of efflux pumps, capable of expelling antimicrobials out of bacterial cells, is one of the most worrisome mechanisms. There has been an ongoing effort to find not only new antimicrobials, but also compounds that can block resistance mechanisms which can be used in combination with approved antimicrobial drugs. In this work, a library of nineteen marine natural products, isolated from marine-derived fungi of the genera Neosartorya and Aspergillus, was evaluated for their potential as bacterial efflux pump inhibitors as well as the antimicrobial-related mechanisms, such as inhibition of biofilm formation and quorum-sensing. Docking studies were performed to predict their efflux pump action. These compounds were also tested for their cytotoxicity in mouse fibroblast cell line NIH/3T3. The results obtained suggest that the marine-derived fungal metabolites are a promising source of compounds with potential to revert antimicrobial resistance and serve as an inspiration for the synthesis of new antimicrobial drugs.

SUBMITTER: Duraes F

PROVIDER: S-EPMC8470461 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Metabolites from Marine-Derived Fungi as Potential Antimicrobial Adjuvants.

Durães Fernando F Szemerédi Nikoletta N Kumla Decha D Pinto Madalena M Kijjoa Anake A Spengler Gabriella G Sousa Emília E

Marine drugs 20210825 9

Marine-derived fungi constitute an interesting source of bioactive compounds, several of which exhibit antibacterial activity. These acquire special importance, considering that antimicrobial resistance is becoming more widespread. The overexpression of efflux pumps, capable of expelling antimicrobials out of bacterial cells, is one of the most worrisome mechanisms. There has been an ongoing effort to find not only new antimicrobials, but also compounds that can block resistance mechanisms which ...[more]

PMID: 34564137

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Project description:Nowadays, endophytic fungi represent a rich source of biological active compounds. In the current study, twelve endophytic fungal species were isolated from Avicennia marina leaves. From the isolates, Aspergillus niger, Penicillium rubens and Alternaria alternata recorded the highest isolation frequency (80%), relative density (12.5%) and antimicrobial activity. The antimicrobial and anticancer activities of P. rubens were more effective than those of A. niger and A. alternata; therefore, its identification was confirmed via the ITS rRNA gene. Filtrate extracts of P. rubens, A. alternata and A. niger were analyzed using GC-MS and showed different detected constituents, such as acetic acid ethyl ester, N-(4,6-Dimethyl-2-pyrimidinyl)-4-(4-nitrobenzylideneamino) benzenesulfonamide, 1,2-benzenedicarboxylic acid, hexadecanoic acid and octadecanoic acid. Filtrate extract of P. rubens exhibited the presence of more compounds than A. alternata and A. niger. Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Candida albicans and Aspergillus fumigatus were more inhibited by P. rubens extract than A. alternata or A. niger, with inhibition zones of 27.2 mm, 22.21 mm, 26.26 mm, 27.33 mm, 28.25 mm and 8.5 mm, respectively. We observed negligible cytotoxicity of P. rubens extract against normal cells of human lung fibroblasts (WI-38 cell line), unlike A. alternata and A. niger extracts. Proliferation of prostate cancer (PC-3) was inhibited using P. rubens extract, exhibiting mortality levels of 75.91% and 76.2% at 200 µg/mL and 400 µg/mL of the extract. Molecular docking studies against the crystal structures of C. albicans (6TZ6) and the cryo-EM structure of B. subtilis (7CKQ) showed significant interactions with benzenedicarboxylic acid and N-(4,6-dimethyl-2-pyrimidinyl)-4-(4-nitrobenzylideneamino) benzenesulfonamide as a constituent of P. rubens extract. N-(4,6-dimethyl-2-pyrimidinyl)-4-(4-nitrobenzylideneamino) benzenesulfonamide had the highest scores of −6.04905 kcal/mol and −6.590 kcal/mol towards (6tz6) and (7CKQ), respectively.

Dataset Information

Metabolites from Marine-Derived Fungi as Potential Antimicrobial Adjuvants.

Publications

Metabolites from Marine-Derived Fungi as Potential Antimicrobial Adjuvants.

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