Polyketides from marine-derived Aspergillus welwitschiae inhibit Staphylococcus aureus virulence factors and

Luciana A Loges1, Denise B Silva2, Gustavo V B Paulino3

  • 1Laboratório de Biofilmes e Diversidade Microbiana (LABDIM), Faculdade de Farmácia and Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul (UFRGS). Av. Ipiranga, 2752, 90610-000, Porto Alegre, Rio Grande do Sul, Brazil.

Microbial Pathogenesis
|February 19, 2020
PubMed

Insights

Natural compounds from Aspergillus welwitschiae show anti-virulence effects against Staphylococcus aureus, reducing biofilm formation and hemolysis. These compounds, combined with vancomycin, offer potential new strategies for combating antibiotic-resistant bacterial infections.

Area of Science:

  • Microbiology
  • Natural Product Chemistry
  • Pharmacology

Background:

  • Staphylococcus aureus is a significant cause of hospital and community infections, with rising antibiotic resistance.
  • S. aureus infections often involve biofilms and virulence factors, making them challenging to treat.
  • Targeting virulence factors offers a strategy to reduce selective pressure for antibiotic resistance.

Purpose of the Study:

  • To investigate the anti-virulence potential of naphtho-γ-pyrones from Aspergillus welwitschiae against Staphylococcus aureus.
  • To characterize the chemical constituents of the isolated compounds.
  • To evaluate the efficacy of these compounds, alone and in combination with vancomycin, in a model of staphylococcal infection.

Main Methods:

  • Extraction and isolation of naphtho-γ-pyrones from Aspergillus welwitschiae mycelium.
  • Chemical characterization using Liquid Chromatography-Diode Array Detection (LC-DAD) and Liquid Chromatography-Mass Spectrometry (LC-MS).
  • Assessment of anti-virulence activities including biofilm inhibition, hemolysis, and coagulation assays.
  • In vivo efficacy testing using the Galleria mellonella infection model, with and without vancomycin.

Main Results:

  • Naphtho-γ-pyrones demonstrated significant anti-virulence activity against Staphylococcus aureus, including a Methicillin-resistant Staphylococcus aureus (MRSA) clinical isolate.
  • Observed reduction in biofilm formation, hemolysis, and coagulation promoted by S. aureus.
  • Combination therapy with vancomycin showed enhanced protection against staphylococcal infection in the Galleria mellonella model.

Conclusions:

  • Natural products, specifically naphtho-γ-pyrones from Aspergillus welwitschiae, represent a promising source for novel anti-virulence agents against Staphylococcus aureus.
  • Anti-virulence strategies and combination therapies offer potential alternatives for managing antibiotic-resistant bacterial infections.
  • Further research into these compounds could lead to new therapeutic approaches for staphylococcal infections.

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