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Differential Susceptibility of Mycoplasma and Ureaplasma Species to Compound-Enhanced Copper Toxicity

Arthur H Totten1, Cameron L Crawford2, Alex G Dalecki2

  • 1Department of Pediatrics, The University of Alabama at Birmingham, Birmingham, AL, United States.

Frontiers in Microbiology
|August 17, 2019
PubMed
Abstract

Insights

Copper-enhanced drug toxicity shows promise for treating human mollicute infections. Disulfiram and neocuproine demonstrated copper-dependent inhibition against Mycoplasma and Ureaplasma species.

Area of Science:

  • Microbiology
  • Drug Discovery
  • Antimicrobial Resistance

Background:

  • Mycoplasmas are significant human pathogens.
  • Antimicrobial resistance necessitates novel drug discovery approaches.
  • Copper ions exhibit antimicrobial properties, requiring bacterial regulation.

Purpose of the Study:

  • To investigate the susceptibility of human mollicutes to copper-induced toxicity.
  • To explore compounds that enhance copper-dependent killing of Mycoplasmas.
  • To identify potential new therapeutic strategies against Mycoplasma and Ureaplasma infections.

Main Methods:

  • Determined minimal inhibitory concentrations (MICs) of copper sulfate (CuSO4) for four human mollicute species.
  • Assessed the MICs of disulfiram (DSF), GTSM, and neocuproine with and without copper.
  • Evaluated the effect of a copper chelator (BCS) on GTSM activity.

Main Results:

  • Human mollicutes exhibited varying tolerance to copper sulfate, with Mycoplasma pneumoniae tolerating higher concentrations.
  • Neocuproine and disulfiram showed copper-dependent growth inhibition across the tested mollicutes.
  • GTSM demonstrated antimicrobial activity, partially dependent on copper levels.

Conclusions:

  • Copper-dependent drug toxicity is a viable strategy for developing new treatments against Mycoplasma and Ureaplasma.
  • Disulfiram and neocuproine are promising candidates for further research in this area.
  • Understanding copper's role in mollicute infections can lead to novel therapeutic interventions.
Keywords:
GTSMMycoplasmaUreaplasmacopperdisulfiramdrug discoverymollicutesneocuproine

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