DNA gyrase and topoisomerase IV mutations in an in vitro fluoroquinolone-resistant Coxiella burnetii strain.
The etiological agent of Q fever, Coxiella burnetii, is an obligate intracellular bacterium that multiplies within a vacuole with lysosomal characteristics. Quinolones have been used as an alternative therapy for Q fever. In this study, quinolone-resistance-determining regions of the genes coding for DNA gyrase and topoisomerase IV were analyzed by DNA sequencing from an in vitro fluoroquinolone-resistant C. burnetii strain (Q212). Sequencing and aligning of DNA gyrase encoding genes (gyrA and gyrB) and topoisomerase IV genes (parC and parE) revealed one gyrA mutation leading to the amino acid substitution Asp87Gly (Escherichia coli numbering), two gyrB mutations leading to the amino acid substitutions Ser431Pro and Met518Ile, and three parC mutations leading to the amino acid substitutions Asp69Asn, Thr80Ile, and Gly104Ser. The corresponding alignment of the C. burnetii Q212 reference strain, the in vitro developed fluoroquinolone-resistant C. burnetii Q212 strain, and E. coli resulted in the identification of several other naturally occurring mutations within and outside the quinolone-resistance-determining regions of C. burnetii providing indications of possible natural resistance to fluoroquinolones. The present study adds additional potential mutations in the DNA topoisomerases that may be involved in fluoroquinolone resistance in C. burnetii due to their previous characterization in other bacterial species.
Vranakis
Iosif
I
Laboratory of Clinical Bacteriology, Parasitology, Zoonoses, and Geographical Medicine (WHO Collaborating Center), Medical School, University of Crete, Heraklion, Greece.
Sandalakis
Vassilios
V
Chochlakis
Dimosthenis
D
Tselentis
Yannis
Y
Psaroulaki
Anna
A
D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D016997:Coxiella burnetii / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000254:growth & development; D027081:DNA Gyrase / Q000235:genetics*; D027101:DNA Topoisomerase IV / Q000235:genetics*; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D024841:Fluoroquinolones / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009154:Mutation; D017422:Sequence Analysis, DNA; D014709:Vero Cells
D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase