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
作者： Ding, Tongyan 1 ; Guo, Zeyu 2 ; Fang, Liangxing 1 ; Guo, Wenying 4 ; Yang, Yuxi 4 ; Li, Yafei 5 ; Li, Xiarong 1 ; He, Limin 1 ;
作者机构： 1.South China Agr Univ, Natl Risk Assessment Lab Antimicrobial Resistance, Guangzhou, Peoples R China
2.Guangdong Lab Lingnan Modern Agr, Guangzhou, Peoples R China
3.Minist Agr & Rural Affairs, Inspect & Testing Ctr Domest Anim Prod Guangzhou, Guangzhou, Peoples R China
4.South China Agr Univ, Coll Vet Med, Guangdong Prov Key Lab Vet Pharmaceut Dev & Safety, Guangzhou, Peoples R China
5.Guangdong Acad Agr Sci, Inst Qual Stand & Monitoring Technol Agroprod, Guangzhou, Peoples R China
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.
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