1887

Abstract

The DNA gyrases from , and bv. , which are species naturally resistant, moderately susceptible and susceptible to fluoroquinolones, respectively, were purified by affinity chromatography on novobiocin-Sepharose columns. The DNA gyrase inhibiting activities (IC values) of classical quinolones and fluoroquinolones were determined from the purified enzymes and were compared to the corresponding antibacterial activities (MICs). Regarding bv. , which is nearly as susceptible as , the corresponding MIC and IC values of quinolones were significantly lower than those found for and (e.g. for ofloxacin, MICs of 025 versus 32 and 1 μg ml, and IC values of 1 versus 8 and 6 μg ml, respectively). Such a result could be related to the presence of Ser-83 in the quinolone-resistance-determining region of the gyrase A subunit of bv. , as found in wild-type , instead of Ala-83 in and , as found in fluoroquinolone-resistant mutants. The IC values of quinolones against the and DNA gyrases were similar, while the corresponding MICs were 32-fold higher for when compared to , suggesting that an additional mechanism, such as a low cell wall permeability or a drug efflux, could contribute to the low antibacterial potency of quinolones against .

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1999-09-01
2024-03-29
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References

  1. Bazile S., Moreau N., Bouzard D., Essiz M. 1992; Relationships among antibacterial activity, inhibition of DNA gyrase, and intracellular accumulation of 11 fluoroquinolones. Antimicrob Agents Chemother 36:2622–2627 [CrossRef]
    [Google Scholar]
  2. Cambau E., Sougakoff W., Jarlier V. 1994; Amplification and nucleotide sequence of the quinolone resistance-determining region in the gyrA gene of mycobacteria. FEMS Microbiol Lett 116:49–54 [CrossRef]
    [Google Scholar]
  3. Cullen M. E., Wyke A. W., Kuroda R., Fisher L. M. 1989; Cloning and characterization of a DNA gyrase A gene from Escherichia coli that confers clinical resistance to 4-quinolones. Antimicrob Agents Chemother 33:886–894 [CrossRef]
    [Google Scholar]
  4. Drlica K., Zhao X. 1997; DNA gyrase, topoisomerase IV, and the 4-quinolones. Microbiol Mol Biol Rev 61:377–392
    [Google Scholar]
  5. Gellert M., Mizuuchi K., O’Dea M. H., Nash H. A. 1976; DNA gyrase: an enzyme that introduces superhelical turns into DNA. Proc Natl Acad Sci USA 73:3872–3876 [CrossRef]
    [Google Scholar]
  6. Gellert M., Mizuuchi K., O’Dea M. H., Itoh T., Tomisawa J. I. 1977; Nalidixic acid resistance: a second genetic character involved in DNA gyrase activity. Proc Natl Acad Sci USA 74:4772–4776 [CrossRef]
    [Google Scholar]
  7. Guillemin I., Cambau E., Jarlier V. 1995; Sequences of conserved region in the A subunit of DNA gyrase from nine species of the genus Mycobacterium: phylogenetic analysis and implication for intrinsic susceptibility to quinolones. Antimicrob Agents Chemother 39:2145–2149 [CrossRef]
    [Google Scholar]
  8. Guillemin I., Jarlier V., Cambau E. 1998; Correlation between quinolone susceptibility patterns and sequences in the A and B subunits of DNA gyrase in mycobacteria. Antimicrob Agents Chemother 42:2084–2088
    [Google Scholar]
  9. Hallet P., Maxwell A. 1991; Novel quinolone resistance mutations of the Escherichia coli DNA gyrase A protein: enzymatic analysis of the mutant proteins. Antimicrob Agents Chemother 35:335–340 [CrossRef]
    [Google Scholar]
  10. Inderlied C. B., Nash K. A. 1996; Antimycobacterial agents: in vitro susceptibility testing, spectra of activity, mechanisms of action and resistance, and assays for activity in biologic fluids. In Antibiotics in Laboratory Medicine pp 127–175Edited by Lorian V. Baltimore: Williams & Wilkins;
    [Google Scholar]
  11. Ito H., Yoshida H., Bogaki-Shonai M., Niga T, Hattori H., Nakamura S. 1994; Quinolone resistance mutations in the DNA gyrase gyrA and gyrB genes of Staphylococcus aureus. Antimicrob Agents Chemother 38:2014–2023 [CrossRef]
    [Google Scholar]
  12. Jarlier V., Nikaido H. 1994; Mycobacterial cell wall: structure and role in natural resistance to antibiotics. FEMS Microbiol Lett 123:11–18 [CrossRef]
    [Google Scholar]
  13. Leysen D. C., Haemers A., Pattyn S. R. 1989; Mycobacteria and the new quinolones. Antimicrob Agents Chemother 33:1–5 [CrossRef]
    [Google Scholar]
  14. Lounis N., Ji B., Truffot-Pernot C., Grosset J. 1995; Selection of clarithromycin-resistant Mycobacterium avium complex during combined therapy using the beige mouse model. Antimicrob Agents Chemother 39:608–612 [CrossRef]
    [Google Scholar]
  15. Madhusudan K., Nagaraja V. 1995; DNA gyrase: cloning and overexpression in Escherichia coli. Microbiology 141:3029–3037 [CrossRef]
    [Google Scholar]
  16. Morais Cabral J. H., Jackson A. P., Smith C. V., Shikotra N., Maxwell A., Liddington R. C. 1997; Crystal structure of the breakage-reunion domain of DNA gyrase. Nature 388:903–906 [CrossRef]
    [Google Scholar]
  17. Moreau N., Robaux H., Baron L., Tabary X. 1990; Inhibitory effects of quinolones on pro- and eucaryotic DNA topoisomerases I and II. Antimicrob Agents Chemother 34:1955–1960 [CrossRef]
    [Google Scholar]
  18. Okuda J., Okamoto S., Takahata M., Nishino T. 1991; Inhibitory effects of ciprofloxacin and sparfloxacin on DNA gyrase purified from fluoroquinolone-resistant strains of methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 35:2288–2293 [CrossRef]
    [Google Scholar]
  19. Rastogi N., Frehel C., Ryter A., Ohayon H., Lesourd M., David H. L. 1981; Multiple drug resistance in Mycobacterium avium: is the wall architecture responsible for the exclusion of antimicrobial agents?. Antimicrob Agents Chemother 20:666–677 [CrossRef]
    [Google Scholar]
  20. Revel V., Cambau E., Jarlier V., Sougakoff W. 1994; Characterization of mutations in Mycobacterium smegmatis involved in resistance to fluoroquinolones. Antimicrob Agents Chemother 38:1991–1996 [CrossRef]
    [Google Scholar]
  21. Revel-Viravau V., Truong Q. C., Moreau N., Jarlier V., Sougakoff W. 1996; Sequence analysis, purification, and study of inhibition by 4-quinolones of the DNA gyrase from Mycobacterium smegmatis. Antimicrob Agents Chemother 40:2054–2061
    [Google Scholar]
  22. Sato K., Inoue Y., Fujii T., Aoyama H., Inoue M., Mitsuhashi S. 1986; Purification and properties of DNA gyrase from a fluoroquinolone-resistant strain of Escherichia coli. Antimicrob Agents Chemother 30:777–780 [CrossRef]
    [Google Scholar]
  23. Snapper S. B., Melton R. E., Mustafa S., Kieser T., Jacobs W. R. 1990; Isolation and characterization of efficient plasmid transformation mutants of Mycobacterium smegmatis. Mol Microbiol 4:1911–1919 [CrossRef]
    [Google Scholar]
  24. Staudenbauer W. L., Orr E. 1981; DNA gyrase: affinity chromatography on novobiocin-Sepharose and catalytic properties. Nucleic Acids Res 9:3589–3603 [CrossRef]
    [Google Scholar]
  25. Sugino A., Peebles C. L., Kreuzer K. N., Cozzarelli N. R. 1977; Mechanism of action of nalidixic acid: purification of Escherichia coli nalA gene product and its relationship to DNA gyrase and a novel nicking-closing enzyme. Proc Natl Acad Sci USA 74:4767–4771 [CrossRef]
    [Google Scholar]
  26. Takiff H. E., Cimino M., Musso M. C., Weisbrod T., Martinez R., Delgado M. B., Salazar L., Bloom B. R., Jacobs W. R. Jr 1996; Efflux pump of the proton antiporter family confers low-level fluoroquinolone resistance in Mycobacterium smegmatis. Proc Natl Acad Sci USA 93:362–366 [CrossRef]
    [Google Scholar]
  27. Wolfson J. S., Hooper D. C. 1989; Fluoroquinolone antimicrobial agents. Clin Microbiol Rev 2:378–424
    [Google Scholar]
  28. Wu L.-C. C., Shahied S. I. 1995; Mycobacterial DNA gyrase: enzyme purification and characterization of supercoiling activity. Arch Biochem Biophys 324:123–129 [CrossRef]
    [Google Scholar]
  29. Xu C., Kreiswirth B. N., Sreevatsan S., Musser J. M., Drlica K. 1996; Fluoroquinolone resistance associated with specific gyrase mutations in clinical isolates of multidrug-resistant Mycobacterium tuberculosis. J Infect Dis 174:1127–1130 [CrossRef]
    [Google Scholar]
  30. Yamagishi J., Yoshida H., Yamayoshi M., Nakamura S. 1986; Nalidixic acid-resistant mutations in the gyrB gene of Escherichia coli. Mol Gen Genet 204:367–373 [CrossRef]
    [Google Scholar]
  31. Yew W. W., Piddock L. J. V., Li M. S. K., Lyon D., Chan C. Y., Cheng A. F. B. 1994; In-vitro activity of quinolones and macrolides against mycobacteria. J Antimicrob Chemother 34:343–351 [CrossRef]
    [Google Scholar]
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