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A Platform of Anti-biofilm Assays Suited to the Exploration of Natural Compound Libraries
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Repurposing bioactive compounds for treating multidrug-resistant pathogens.

Nicholas A Hummell1, Natalia V Kirienko1

  • 1Department of BioSciences, Rice University, Houston, Texas, USA.

Journal of Medical Microbiology
|March 13, 2020
PubMed
Summary

Drug repurposing offers a path against rising antimicrobial resistance. Two compounds, DMAQ-B1 and CD437, showed promise in rescuing *C. elegans* from bacterial infections, though toxicity limits their use.

Keywords:
AntimicrobialsC. elegansDrug RepositioningP. aeruginosa

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Area of Science:

  • Microbiology
  • Drug Discovery
  • Toxicology

Background:

  • Antimicrobial resistance (AMR) is a growing global health threat, outpacing new drug development.
  • Drug repurposing presents a cost-effective strategy to identify novel antimicrobial agents from existing compounds.
  • High-throughput screening in model organisms can accelerate the discovery of potential drug candidates.

Purpose of the Study:

  • To evaluate the antimicrobial properties of five known bioactive compounds (DMAQ-B1, carboplatin, oxaliplatin, CD437, PSB-069).
  • To assess the efficacy of these compounds against *Pseudomonas aeruginosa*, *Enterococcus faecalis*, and *Staphylococcus aureus*.
  • To investigate potential synergistic effects with conventional antibiotics and evaluate compound toxicity.

Main Methods:

  • Colony-forming unit (c.f.u.) assays and biofilm staining were used to assess antimicrobial activity.
  • Checkerboard assays were employed to determine synergy with existing antibiotics.
  • *Caenorhabditis elegans* models were utilized for efficacy and toxicity testing against bacterial pathogens.

Main Results:

  • Four compounds demonstrated efficacy in rescuing *C. elegans* from a secondary bacterial pathogen.
  • DMAQ-B1 and CD437 showed efficacy against all three tested pathogens (*P. aeruginosa*, *E. faecalis*, *S. aureus*).
  • Platinum complexes exhibited enhanced antimicrobial activity against *P. aeruginosa*; CD437 showed minor synergy with ampicillin, but DMAQ-B1 and CD437 displayed mammalian cell toxicity.

Conclusions:

  • DMAQ-B1 and CD437 show potential for drug repurposing against bacterial infections, despite observed toxicity.
  • The study highlights the utility of *C. elegans* as a model for preliminary antimicrobial screening of bioactive compounds.
  • Further research is needed to mitigate toxicity and optimize these compounds for therapeutic applications.