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Metabolites from Marine-Derived Fungi as Potential Antimicrobial Adjuvants
Fernando Durães1,2, Nikoletta Szemerédi3, Decha Kumla2,4
1Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
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.
Insights
Marine fungi yield compounds that combat bacterial efflux pumps, a key mechanism in antimicrobial resistance. These natural products show potential for developing new drugs to overcome drug-resistant infections.
Area of Science:
- Marine microbiology
- Natural product chemistry
- Antimicrobial resistance
Background:
- Marine-derived fungi are a rich source of bioactive compounds with antibacterial properties.
- Antimicrobial resistance, particularly via efflux pump overexpression, is a growing global health concern.
- There is a critical need for novel antimicrobials and agents that can restore the efficacy of existing drugs.
Purpose of the Study:
- To evaluate marine natural products from *Neosartorya* and *Aspergillus* fungi as inhibitors of bacterial efflux pumps.
- To investigate their potential in inhibiting biofilm formation and quorum-sensing.
- To assess their cytotoxicity and predict their efflux pump action through docking studies.
Main Methods:
- Isolation and evaluation of nineteen marine natural products.
- Testing for antibacterial activity, efflux pump inhibition, biofilm inhibition, and quorum-sensing inhibition.
- Computational docking studies to predict efflux pump interactions.
- Cytotoxicity assessment using the NIH/3T3 mouse fibroblast cell line.
Main Results:
- Several marine natural products demonstrated potential as bacterial efflux pump inhibitors.
- Some compounds showed activity against biofilm formation and quorum-sensing pathways.
- Docking studies provided insights into potential efflux pump inhibition mechanisms.
- Compounds exhibited varying levels of cytotoxicity in the tested cell line.
Conclusions:
- Marine-derived fungal metabolites represent a promising resource for discovering compounds that can reverse antimicrobial resistance.
- These natural products can serve as a basis for the design and synthesis of novel antimicrobial agents.
- Further research into these compounds could lead to new strategies for combating drug-resistant bacteria.
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