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Characterization of Salmonella Typhimurium DNA gyrase as a target of quinolones
| Title: | Characterization of Salmonella Typhimurium DNA gyrase as a target of quinolones |
| Authors: | Kongsoi, Siriporn Browse this author | | Yokoyama, Kazumasa Browse this author | | Suprasert, Apinun Browse this author | | Utrarachkij, Fuangfa Browse this author | | Nakajima, Chie Browse this author →KAKEN DB | | Suthienkul, Orasa Browse this author | | Suzuki, Yasuhiko Browse this author →KAKEN DB |
| Keywords: | DNA gyrase | | Quinolones | | Salmonella Typhimurium |
| Issue Date: | Aug-2015 |
| Publisher: | John Wiley & Sons |
| Journal Title: | Drug Testing and Analysis |
| Volume: | 7 |
| Issue: | 8 |
| Start Page: | 714 |
| End Page: | 720 |
| Publisher DOI: | 10.1002/dta.1744 |
| PMID: | 25381884 |
| Abstract: | Quinolones exhibit good antibacterial activity against Salmonella spp. isolates and are often the choice of treatment for life-threatening salmonellosis due to multi-drug resistant strains. To assess the properties of quinolones, we performed an in vitro assay to study the antibacterial activities of quinolones against recombinant DNA gyrase. We expressed the S. Typhimurium DNA gyrase A (GyrA) and B (GyrB) subunits in Escherichia coli. GyrA and GyrB were obtained at high purity (>95%) by nickel-nitrilotriacetic acid agarose resin column chromatography as His-tagged 97-kDa and 89-kDa proteins, respectively. Both subunits were shown to reconstitute an ATP-dependent DNA supercoiling activity. Drug concentrations that suppressed DNA supercoiling by 50% (IC50s) or generated DNA cleavage by 25% (CC25s) demonstrated that quinolones highly active against S. Typhimurium DNA gyrase share a fluorine atom at C-6. The relationships between the minimum inhibitory concentrations (MICs), IC50s and CC25s were assessed by estimating a linear regression between two components. MICs measured against S. Typhimurium NBRC 13245 correlated better with IC50s (R = 0.9988) than CC25s (R = 0.9685). These findings suggest that the DNA supercoiling inhibition assay may be a useful screening test to identify quinolones with promising activity against S. Typhimurium. The quinolone structure-activity relationship demonstrated here shows that C-8, the C-7 ring, the C-6 fluorine, and N-1 cyclopropyl substituents are desirable structural features in targeting S. Typhimurium gyrase. |
| Rights: | This is the peer reviewed version of the following article: Siriporn Kongsoi, Kazumasa Yokoyama, Apinun Suprasert, Fuangfa Utrarachkij, Chie Nakajima, Orasa Suthienkul,Yasuhiko Suzuki. Characterization of Salmonella Typhimurium DNA gyrase as a target of quinolones. Drug Test Anal. 2015;7:714-720, which has been published in final form at https://doi.org/10.1002/dta.1744. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/76491 |
| Appears in Collections: | 人獣共通感染症国際共同研究所 (International Institute for Zoonosis Control) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
国際連携研究教育局 : GI-CoRE (Global Institution for Collaborative Research and Education : GI-CoRE) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 鈴木 定彦
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