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Characterization of Salmonella Typhimurium DNA gyrase as a target of quinolones
Kongsoi S. - ไม่ระบุหน่วยงาน
ชื่อเรื่อง (EN): Characterization of Salmonella Typhimurium DNA gyrase as a target of quinolones
ผู้แต่ง / หัวหน้าโครงการ (EN): Kongsoi S.
บทคัดย่อ (EN): 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. © 2014 John Wiley & Sons, Ltd.
บทคัดย่อ: ไม่พบข้อมูลจากหน่วยงานต้นทาง
ภาษา (EN): en
เอกสารแนบ (EN): https://www.scopus.com/inward/record.uri?eid=2-s2.0-84938798410&doi=10.1002%2fdta.1744&partnerID=40&md5=19755d4c947833227c8645154383fa3f
เผยแพร่โดย (EN): มหาวิทยาลัยมหิดล
คำสำคัญ (EN): Topoisomerase II Inhibitors
เจ้าของลิขสิทธิ์ (EN): มหาวิทยาลัยมหิดล
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Characterization of Salmonella Typhimurium DNA gyrase as a target of quinolones
Kongsoi S.
มหาวิทยาลัยมหิดล
ไม่ระบุวันที่เผยแพร่
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