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Fedorchuk V. V., Grudinina S. A., Krotova L. A., Cherkashin Ye. A., Sidorenko S. V., Tishkov V. I.
Role of Mutations in DNA-Gyrase and Topoisomerase IV in Resistance of Streptococcus
Pneumoniae to Fluoroquinolones
Abstract
Streptococcus pneumoniae is an important human pathogen that cause
respiratory illnesses such as pneumonia and other serious diseases, including
meningitis and otitis. Like that increased use of quinolones in last years
resulted in pneumococci with decreased drug susceptibility. Resistance to
quinolones often involves mutation of DNA gyrase and then of topoisomerase IV.
Quinolones are thought to form a topoisomerase-drug-DNA ternary complex that
cellular processes convert into a lethal lesion, possibly a double-stranded DNA
break. Resistance mutations occur in a short discrete segment of the DNA gyrase
gyrA and gyrB genes and the topoisomerase IV parC and parE
genes, named the quinolone resistance determining region (QRDR). A number
of isolates of S.pneumoniae from Moscow clinics showing reduced
susceptibility or resistance to fluoroquinolones were characterized by
antimicrobial susceptibility, and genetic analyses of the QRDRs of gyrA,
gyrB, parC, and parE. Genes fragments that included the
QRDRs were prepared by PCR with specific primers and. DNA and corresponding
amino acid sequences were determined and analyzed.
Copyright (C) Chemistry Dept., Moscow State University, 2002
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