Synergistic antibacterial effects of closantel and its enantiomers in combination with colistin against multidrug resistant gram-negative bacteria

文献类型： 外文期刊

第一作者： Ding, Tongyan

作者： Ding, Tongyan;Fang, Liangxing;Li, Xiarong;He, Limin;Guo, Zeyu;He, Limin;Fang, Liangxing;Li, Xiarong;He, Limin;Guo, Wenying;Yang, Yuxi;He, Limin;Li, Yafei

作者机构：

关键词： closantel; stereoselectivity; colistin; reverse drug resistance; gram-negative bacteria

期刊名称：FRONTIERS IN MICROBIOLOGY （ 影响因子：5.2； 五年影响因子：6.2 ）

ISSN：

年卷期： 2024 年 15 卷

页码：

收录情况： SCI

摘要： Drug combinations and repurposing have recently provided promising alternatives to cope with the increasingly severe issue of antibiotic resistance and depletion of natural drug molecular repertoires that undermine traditional antibacterial strategies. Closantel, an effective adjuvant, reverses antibiotic resistance in gram-negative bacteria. Herein, the combined antibacterial enantioselectivity of closantel is presented through separate enantiomer studies. Despite yielding unexpected differences, two closantel enantiomers (R, S) increased colistin activity against gram-negative bacteria both in vitro and in vivo. The fractional inhibitory concentration indices of R-closantel and S-closantel combined with colistin against Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli ranged from 0.0087 to 0.5004 and from 0.0117 to 0.5312, respectively. This difference was further demonstrated using growth inhibition assays and time-killing curves. Mechanistically, a higher intracellular concentration of R-CLO is more effective in enhancing the antimicrobial activity of combination. A mouse cutaneous infection model confirmed the synergistic stereoselectivity of closantel. This discovery provides novel insights for developing precision medication and containment of increasing antibiotic resistance.

分类号：

  • 相关文献
作者其他论文 更多>>

微信小程序