Metabolites from Marine-Derived Fungi as Potential Antimicrobial Adjuvants

Mar Drugs. 2021 Aug 25;19(9):475. doi: 10.3390/md19090475.

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.

Keywords: antimicrobial activity; biofilm inhibition; efflux pump inhibition; marine-derived fungal metabolites; quorum-sensing inhibition.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Aspergillus / metabolism*
  • Bacterial Proteins / metabolism
  • Biofilms / drug effects
  • Biofilms / growth & development
  • Biological Products / pharmacology*
  • Cell Survival / drug effects
  • Membrane Transport Proteins / metabolism
  • Mice
  • Microbial Sensitivity Tests
  • Molecular Docking Simulation
  • NIH 3T3 Cells
  • Neosartorya / metabolism*
  • Salmonella enterica / drug effects
  • Salmonella enterica / growth & development
  • Salmonella enterica / metabolism
  • Staphylococcus aureus / drug effects
  • Staphylococcus aureus / growth & development
  • Staphylococcus aureus / metabolism
  • Staphylococcus aureus / physiology

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Biological Products
  • Membrane Transport Proteins