Alterations in DNA gyrase and topoisomerase IV in resistant mutants of Clostridium perfringens found after in vitro treatment with fluoroquinolones.
Article Details
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Rafii F, Park M, Novak JS
Alterations in DNA gyrase and topoisomerase IV in resistant mutants of Clostridium perfringens found after in vitro treatment with fluoroquinolones.
Antimicrob Agents Chemother. 2005 Feb;49(2):488-92.
- PubMed ID
- 15673722 [ View in PubMed]
- Abstract
To compare mutations in the DNA gyrase (gyrA and gyrB) and topoisomerase IV (parC and parE) genes of Clostridium perfringens, which are associated with in vitro exposure to fluoroquinolones, resistant mutants were selected from eight strains by serial passage in the presence of increasing concentrations of norfloxacin, ciprofloxacin, gatifloxacin, or trovafloxacin. The nucleotide sequences of the entire gyrA, gyrB, parC, and parE genes of 42 mutants were determined. DNA gyrase was the primary target for each fluoroquinolone, and topoisomerase IV was the secondary target. Most mutations appeared in the quinolone resistance-determining regions of gyrA (resulting in changes of Asp-87 to Tyr or Gly-81 to Cys) and parC (resulting in changes of Asp-93 or Asp-88 to Tyr or Ser-89 to Ile); only two mutations were found in gyrB, and only two mutations were found in parE. More mutants with multiple gyrA and parC mutations were produced with gatifloxacin than with the other fluoroquinolones tested. Allelic diversity was observed among the resistant mutants, for which the drug MICs increased 2- to 256-fold. Both the structures of the drugs and their concentrations influenced the selection of mutants.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Gatifloxacin DNA gyrase subunit A Protein Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4) YesInhibitorDetails Gatifloxacin DNA gyrase subunit B Protein Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4) YesInhibitorDetails Gatifloxacin DNA topoisomerase 4 subunit A Protein Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4) YesInhibitorDetails Gatifloxacin DNA topoisomerase 4 subunit B Protein Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4) YesInhibitorDetails Norfloxacin DNA topoisomerase 4 subunit A Protein Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd) YesInhibitorDetails Pefloxacin DNA topoisomerase 4 subunit A Protein Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd) YesInhibitorDetails Trovafloxacin DNA topoisomerase 4 subunit A Protein Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd) YesInhibitorDetails