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Modulation of gyrase-mediated DNA cleavage and cell killing by ATP

T K Li1, L F Liu

  • 1Department of Pharmacology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway 08854, USA.

Antimicrobial Agents and Chemotherapy
|May 21, 1998
PubMed

Insights

Cellular ATP levels regulate bacterial susceptibility to gyrase poisons like antibiotics. Lowering ATP protects E. coli from these bactericidal agents by modulating DNA gyrase activity.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Biochemistry

Background:

  • Gyrase poisons, including quinolone antibiotics and epipodophyllotoxins, are bactericidal agents.
  • Cellular energy status, particularly the ATP pool, may influence bacterial response to these agents.

Purpose of the Study:

  • To investigate the role of cellular ATP levels in the bactericidal action of gyrase poisons.
  • To elucidate the mechanism by which ATP influences DNA gyrase activity in the presence of these poisons.

Main Methods:

  • Utilized Escherichia coli cells and purified E. coli DNA gyrase.
  • Assessed the protective effects of ATP-lowering agents (2,4-dinitrophenol, fluoroacetic acid) against gyrase poisons.
  • Examined the impact of ATP and ADP concentrations on gyrase-mediated DNA cleavage in vitro.

Main Results:

  • ATP significantly stimulates gyrase-mediated DNA cleavage in the presence of quinolones and epipodophyllotoxins.
  • The ATP/ADP ratio modulates DNA cleavage, with higher ratios increasing cleavage.
  • Coumermycin A1, an ATPase inhibitor, antagonized ATP's effect and protected cells, similar to ATP-lowering agents.

Conclusions:

  • Cellular susceptibility to gyrase poisons is determined by the ATP/ADP ratio.
  • This ratio modulates gyrase-mediated DNA cleavage, impacting bacterial survival.

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