Quinolone-Resistant Mutations of DNA Gyrase Increase Sensitivity to Acriflavine

• Published in: Biological & pharmaceutical bulletin Vol. 21; no. 7; pp. 667 - 672
• Main Authors: FUNATSUKI, Kenzo, TANAKA, Reiji, INAGAKI, Shuichiro, KONNO, Haruyoshi, KATOH, Kenji, NAKAMURA, Hakobu
• Format: Journal Article
• Language: English
• Published: Tokyo The Pharmaceutical Society of Japan 01.07.1998; Maruzen; Japan Science and Technology Agency
• Subjects: 4-Quinolones; acrB; Acriflavine - pharmacology; Anti-Infective Agents - pharmacology; Anti-Infective Agents, Local - pharmacology; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Biological and medical sciences; Cloning, Molecular; DNA binding; DNA Topoisomerases, Type II - genetics; DNA Topoisomerases, Type II - metabolism; DNA, Bacterial - drug effects; DNA, Bacterial - metabolism; DNA-Binding Proteins - antagonists & inhibitors; DNA-Binding Proteins - metabolism; Drug Resistance, Microbial - genetics; E. coli; Enzyme Inhibitors - pharmacology; Escherichia coli - drug effects; Escherichia coli - enzymology; Escherichia coli - genetics; Medical sciences; Mutagenesis; Pharmacology. Drug treatments; Protein Binding; supercoiling; topoisomerase II; Topoisomerase II Inhibitors; DNA topoisomerase (ATP-hydrolysing); Oxolinic acid; Enzyme; Escherichia coli; In vitro; Resistance; Isomerases; Sensitivity resistance; DNA; Covalent bond; Bacteria; Genetics; Mutation; Antibacterial agent; Mechanism of action; Quinolone derivatives; Enterobacteriaceae
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.21.667

DNA gyrases were constructed to posses the quinolone-resistant (D87N in GyrA or K447E in GyrB) and acrB (S759R-R760C in GyrB) mutations and their sensitivities to acriflavine and oxolinic acid were examined. Both quinolone-resistant mutations in GyrA and GyrB increased acriflavine sensitivities in the supercoiling assay irrespective of the co-presence of the acrB mutation. In the DNA binding assay, however, the hypersensitivity caused by the GyrB (K447E) mutation was observed only in the co-presence of the acrB mutation; the presence of the acrB mutation, which not affecting acriflavine sensitivity, reduces the extent of DNA binding, as reported previously. Thus, the quinolone-resistant mutation site in GyrB is likely to be involved in DNA binding which is not detectable in acrB+ gyrase. Furthermore, oxolinic acid was found to enhance DNA binding of the gyrase having GyrB (acrB-K447E), supporting a recent proposal that quinolone binding to the DNA-gyrase complex does not require DNA breakage.