DNA intercalating drugs inhibit positive supercoiling induced by novobiocin in halophilic archaea

D Gadelle1, P Forterre

  • 1Institute de Génétique et Microbiologie, Université Paris-Sud, CNRS, URA 1352, Orsay, France.

FEMS Microbiology Letters
|October 15, 1994
PubMed

Insights

DNA intercalators like actinomycin D and ellipticine, and DAPI, inhibit haloarchaeon growth and bind to its plasmid. These compounds offer a novel method for prescreening DNA intercalators and understanding drug actions in archaea.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Genetics

Background:

  • Haloarchaea possess unique plasmids, such as pGRB-1 in Halobacterium sp. GRB.
  • Understanding drug interactions with archaeal DNA is crucial for antimicrobial development.
  • DNA topoisomerase II inhibitors are known to affect DNA structure and function.

Purpose of the Study:

  • To investigate the effects of DNA intercalators and a minor groove ligand on haloarchaeal growth and plasmid DNA.
  • To determine if these compounds induce DNA damage or alter supercoiling in Halobacterium sp. GRB.
  • To explore the potential of haloarchaeal plasmids as a tool for drug screening.

Main Methods:

  • Treatment of Halobacterium sp. GRB with actinomycin D, 2-methyl-9-hydroxy-ellipticine, and DAPI.
  • Analysis of plasmid pGRB-1 for double-strand breaks and supercoiling changes.
  • Assessment of growth inhibition in response to drug treatment.

Main Results:

  • Actinomycin D, ellipticine, and DAPI inhibited Halobacterium sp. GRB growth and bound to plasmid pGRB-1.
  • Unlike topoisomerase II inhibitors, these compounds did not cause DNA breaks or relaxation.
  • DNA intercalators inhibited positive supercoiling induced by novobiocin, suggesting transcription-driven supercoiling.

Conclusions:

  • Haloarchaeal plasmids can be used to prescreen for DNA intercalators.
  • The mode of action of different drug families can be discriminated using haloarchaeal plasmids.
  • Transcription likely drives positive supercoiling in haloarchaea, similar to Bacteria.

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