Guanethidine Restores Tetracycline Sensitivity in Multidrug-Resistant Carrying Gene.

Xiaoou Zhao, Mengna Zhang, Zhendu Zhang, Lei Wang, Yu Wang, Lizai Liu, Duojia Wang, Xin Zhang, Luobing Zhao, Yunhui Zhao, Xiangshu Jin, Xiaoxiao Liu, Hongxia Ma
Author Information
  1. Xiaoou Zhao: College of Animal Science and Technology, Jilin Agricultural University, Xincheng Street No. 2888, Changchun 130118, China. ORCID
  2. Mengna Zhang: College of Animal Science and Technology, Jilin Agricultural University, Xincheng Street No. 2888, Changchun 130118, China.
  3. Zhendu Zhang: Institute of Animal Husbandry and Veterinary Medicine, Jilin Academy of Agricultural Science, Kemao Street No. 186, Gongzhuling 136100, China.
  4. Lei Wang: Institute of Animal Husbandry and Veterinary Medicine, Jilin Academy of Agricultural Science, Kemao Street No. 186, Gongzhuling 136100, China.
  5. Yu Wang: College of Animal Science and Technology, Jilin Agricultural University, Xincheng Street No. 2888, Changchun 130118, China. ORCID
  6. Lizai Liu: Institute of Animal Husbandry and Veterinary Medicine, Jilin Academy of Agricultural Science, Kemao Street No. 186, Gongzhuling 136100, China.
  7. Duojia Wang: Institute of Animal Husbandry and Veterinary Medicine, Jilin Academy of Agricultural Science, Kemao Street No. 186, Gongzhuling 136100, China.
  8. Xin Zhang: Institute of Animal Husbandry and Veterinary Medicine, Jilin Academy of Agricultural Science, Kemao Street No. 186, Gongzhuling 136100, China.
  9. Luobing Zhao: Institute of Animal Husbandry and Veterinary Medicine, Jilin Academy of Agricultural Science, Kemao Street No. 186, Gongzhuling 136100, China.
  10. Yunhui Zhao: Institute of Animal Husbandry and Veterinary Medicine, Jilin Academy of Agricultural Science, Kemao Street No. 186, Gongzhuling 136100, China.
  11. Xiangshu Jin: Institute of Animal Husbandry and Veterinary Medicine, Jilin Academy of Agricultural Science, Kemao Street No. 186, Gongzhuling 136100, China.
  12. Xiaoxiao Liu: Institute of Animal Husbandry and Veterinary Medicine, Jilin Academy of Agricultural Science, Kemao Street No. 186, Gongzhuling 136100, China.
  13. Hongxia Ma: College of Animal Science and Technology, Jilin Agricultural University, Xincheng Street No. 2888, Changchun 130118, China. ORCID

Abstract

The worrying issue of antibiotic resistance in pathogenic bacteria is aggravated by the scarcity of novel therapeutic agents. Antibiotic adjuvants offer a promising solution due to their cost-effectiveness and high efficacy in addressing this issue, such as the β-lactamase inhibitor sulbactam (a β-lactam adjuvant) and the dihydrofolate reductase inhibitor trimethoprim (a sulfonamide adjuvant). This study aimed to discover potential adjuvants for tetracyclines from a list of previously approved drugs to restore susceptibility to carrying the gene. We have screened guanethidine, a compound from the Chinese pharmacopoeia, which effectively potentiates the activity of tetracyclines by reversing resistance in -positive , enhancing its antibacterial potency, and retarding the development of resistance. Guanethidine functions via the inhibition of the TetA efflux pump, thereby increasing the intracellular concentration of tetracyclines. Our findings suggest that guanethidine holds promise as an antibiotic adjuvant.

Keywords

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Grants

  1. CXGC2023RCG008/Jilin Province Agricultural Science and Technology Innovation Project
  2. YDZJ202203CGZH050, 20210202033NC, 20220202060NC, 20220202050NC, 20220502004GH/Jilin Provincial Science and Technology Development Project

Word Cloud

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