Substitutions of amino acids in α-helix-4 of gyrase A confer fluoroquinolone resistance on Clostridium perfringens

DNA gyrase, an essential enzyme that regulates DNA topology in bacteria, is the target of fluoroquinolones. Three fluoroquinolone-resistant mutants derived from one strain of Clostridium perfringens had amino acid substitutions of glycine 81 to cysteine, aspartic acid 87 to tyrosine, or both, in α-h...

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Bibliographic Details
Published in:Archives of microbiology 2007-02, Vol.187 (2), p.137-144
Main Authors: Rafii, Fatemeh, Park, Miseon
Format: Article
Language:English
Subjects:
Amino Acid Substitution - drug effects
Amino Acid Substitution - genetics
Anti-Infective Agents - pharmacology
Bacteriology
Biological and medical sciences
Clostridium
Clostridium perfringens
Clostridium perfringens - drug effects
Clostridium perfringens - enzymology
Clostridium perfringens - metabolism
DNA Gyrase - genetics
DNA Gyrase - physiology
DNA, Bacterial - chemistry
DNA, Bacterial - genetics
Drug Resistance, Bacterial - genetics
Fluoroquinolones
Fluoroquinolones - pharmacology
Fundamental and applied biological sciences. Psychology
Gyrase A
Metabolism. Enzymes
Microbial Sensitivity Tests
Microbiology
mutation
Resistance
Structure-Activity Relationship
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Summary:DNA gyrase, an essential enzyme that regulates DNA topology in bacteria, is the target of fluoroquinolones. Three fluoroquinolone-resistant mutants derived from one strain of Clostridium perfringens had amino acid substitutions of glycine 81 to cysteine, aspartic acid 87 to tyrosine, or both, in α-helix-4 of gyrase A. The gyrase mutations affected the growth kinetics of mutants differently when the mutants were exposed to increasing concentrations of gatifloxacin and ciprofloxacin. Fluoroquinolone concentration-dependent effects observed during growth in the exponential and stationary phases depended on the presence of particular gyrA mutations. Introduction of a wild-type gyrA gene into the mutants enhanced their susceptibility to fluoroquinolones and decreased their growth rates proportional to increases in fluoroquinolone concentrations. Amino acid substitutions in α-helix-4 of gyrase A protected C. perfringens from fluoroquinolones, and a strain with two substitutions was the most resistant.
ISSN:0302-8933
1432-072X
DOI:10.1007/s00203-006-0180-y