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

Tsai Kun Li, Leroy-Fong Liu

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

An uncoupler of oxidative phosphorylation, 2,4-dinitrophenol, and an aconitase inhibitor, fluoroacetic acid, both of which are known to lower the cellular ATP pool, protected Escherichia call cells from the bactericidal actions of gyrase poisons including quinolone antibiotics, nalidixic acid and ciprofloxacin, and the epipodophyllotoxins VP-16 and VM-26. Using purified E. coli DNA gyrase, we examined the effect of ATP on gyrase-mediated DNA cleavage in the presence of these gyrase poisons. ATP was shown to stimulate gyrase-mediated DNA cleavage from 10- to more than 100-fold in the presence of these gyrase poisons. ADP antagonized the stimulatory effect of ATP. Consequently, gyrase-mediated DNA cleavage induced by gyrase poisons is modulated by the ATP concentration/ADP concentration ([ATP]/[ADP]) ratio. Coumermycin A1, an inhibitor of the ATPase subunit of DNA gyrase, like ADP, also effectively antagonized the stimulatory effect of ATP on gyrase-mediated DNA cleavage induced by gyrase poisons. Furthermore, coumermycin A1, like DNP and fluoroacetic acid, also protected cells from the bactericidal action of gyrase poisons. In the aggregate, our results are consistent with the notion that the [ATP]/[ADP] ratio, through its modulatory effect on the gyrase- mediated DNA cleavage, is an important determinant of cellular susceptibility to gyrase poisons.

Original languageEnglish
Pages (from-to)1022-1027
Number of pages6
JournalAntimicrobial Agents and Chemotherapy
Volume42
Issue number5
Publication statusPublished - May 1998
Externally publishedYes

Fingerprint

DNA Cleavage
Poisons
Adenosine Triphosphate
Adenosine Diphosphate
DNA Gyrase
Teniposide
Podophyllotoxin
Aconitate Hydratase
2,4-Dinitrophenol
Escherichia
Nalidixic Acid
Oxidative Phosphorylation
Quinolones
Etoposide
Ciprofloxacin
Adenosine Triphosphatases
Escherichia coli
Anti-Bacterial Agents

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Modulation of gyrase-mediated DNA cleavage and cell killing by ATP. / Li, Tsai Kun; Liu, Leroy-Fong.

In: Antimicrobial Agents and Chemotherapy, Vol. 42, No. 5, 05.1998, p. 1022-1027.

Research output: Contribution to journalArticle

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