Journal of Antimicrobial Chemotherapy (2000) 45, 771-775
© 2000 The British Society for Antimicrobial Chemotherapy
Comparison of gyrA and parC mutations and resistance levels among fluoroquinolone-resistant isolates and laboratory-derived mutants of oral streptococci
a Department of Oral Surgery, School of Medicine, Tokai University, Bouseidai, Isehara, Kanagawa, 259-1193 Japan; b Department of Genetics, and c Chemotherapy Division, Mitsubishi Kagaku Bio-Clinical Laboratories Inc., 3-30-1 Shimura, Itabashi-ku, Tokyo, 174-8555 Japan
Laboratory-derived fluoroquinolone-resistant mutants were obtained by serial passage of Streptococcus sanguis and Streptococcus anginosus isolates on agar containing increasing concentrations of old and new fluoroquinolones, ofloxacin and DU-6859a, respectively. Sequencing of an S. sanguis isolate exposed to DU-6859a showed that resistance was associated with two mutations in the quinolone resistance determining region (QRDR) of the gyrA gene (Ser83
Phe; Glu87
Lys), and with a mutation in the parC gene (Ser79
Ile). However, different mutations in the gyrA gene (Ser83
Tyr) and parC gene (Ser79
Phe) were found in a S. sanguis isolate exposed to ofloxacin. A fluoroquinolone-resistant isolate, QR-95101, from a dental infection, had a single mutation in the gyrA gene (Ser83
Phe) and in the parC gene (Ser79
Phe). Two fluoroquinolone-resistant mutants, QS-701OFm and QS-701DUm, were obtained from S. anginosus QS-701, by exposure to ofloxacin and DU-6859a, respectively. These mutants showed a common substitution at codon 83 (Ser
Phe) in the gyrA gene but had different substitutions at codon 87 (QS-701OFm, Glu
Gln; QS-701DUm, Glu
Lys). They also had different substitutions at codons 79 and 135 in the parC gene (QS-701OFm, Ser79
Leu but no change at Glu135; QS-701DUm, Ser79
Ile and Glu135
Gln). The resistance levels of the DU-6859a-selected resistant S. sanguis mutant QS-951DUm to DU-6859a, ofloxacin, ciprofloxacin and norfloxacin were higher than those of the ofloxacin-selected resistant mutant QS-951OFm. However, ampicillin susceptibilities of these mutants were not different from the parental strains. In S. anginosus, the DU-6859a-selected fluoroquinolone-resistant mutant QS-701DUm was resistant to all the fluoroquinolones tested, while the ofloxacin-selected mutant QS-701OFm was resistant to three fluoroquinolones, but not DU-6859a. The results indicate that different fluoroquinolones select distinct mutations in the QRDR of the gyrA and parC genes in oral streptococci. The gyrA or parC mutation in oral streptococci may determine the levels of fluoroquinolone resistance.
* Corresponding author. Tel: +81-463-93-1121; Fax: +81-463-91-5902; E-mail: akihiro{at}is.icc.u-tokai.ac.jp
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