Genetic study of the mechanisms of action of fluoroquinolones in Streptococcus pneumoniae.
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Accession number;00A0471422
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| Title;Genetic study of the mechanisms of action of fluoroquinolones in Streptococcus pneumoniae. |
| Author;
FUKUDA HIDEYUKI
(Kyorin Pharm. Co., Ltd., Cent. Lab.)
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Journal Title;Japanese Journal of Chemotherapy
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Journal Code:F0608A
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ISSN:1340-7007
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VOL.48;NO.4;PAGE.243-250(2000)
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| Figure&Table&Reference;FIG.1, TBL.4, REF.27 |
| Pub. Country;Japan |
| Language;Japanese |
| Abstract;Fluoroquinolonc-resistant mutant strains were sequentially isolated from the wild-type Streptococcus pneumoniae IID 553 by selection with various fluoroquinolones. The first-step mutant strains, which were obtained by selection with trovafloxacin (TVFX), levofloxacin (LVFX), norfloxacin (NFLX) and ciprofloxacin (CPFX), possessed single point mutations in the parC gene. These parC mutant strains had decreased in susceptibilities to the selecting agents. Other first-step mutant strains, which were obtained by selection with gatifloxacin (GFLX) and sparfloxacin (SPFX), possessed single point mutations in the gyrA gene. These gyrA mutant strains had decreased in susceptibility to GFLX and SPFX but not to the other fluoroquinolones. The second-step mutant strains obtained from the first-step parC and gyrA mutant strains possessed additional gyrA and parC mutations, respectively. As a result, all of the second-step mutant strains possessed both gyrA and parC mutations. The susceptibilities of the second-step mutant strains to all of the fluoroquinolones were lower than those of the first-step mutant strains. These results suggest that in wild-type S. pneumoniae the primary target of TVFX, LVFX, NFLX and CPFX is topoisomerase IV, whereas the primary target of GFLX and SPFX is DNA gyrase, and in the parC and gyrA mutant strains the primary target of all the quinolones are DNA gyrase and topoisomerase IV, respectively. The frequencies of appearance of the first- and the second-step mutant strains were different among the fluoroquinolones used for selection. Moreover, the fluoroquinolones which selected mutant strains with a low frequency showed slight decreased activity against the mutant strains obtained. These results suggest that the fluoroquinolones which select the mutant strains with a low frequency inhibit both DNA gyrase and topoisomerase IV at nearly the same levels in S. pneumoniae.... (author abst.) |
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