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

• 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
• ISSN: 0302-8933; 1432-072X
• DOI: 10.1007/s00203-006-0180-y

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.