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Characterization of Salmonella Typhimurium DNA gyrase as a target of quinolones

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Please use this identifier to cite or link to this item:http://hdl.handle.net/2115/76491

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:人獣共通感染症リサーチセンター (Research Center 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)

Submitter: 鈴木 定彦

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