Guanethidine Restores Tetracycline Sensitivity in Multidrug-Resistant Escherichia coli Carrying tetA Gene.

IF 4.3 2区医学 Q1 INFECTIOUS DISEASES Antibiotics-Basel Pub Date : 2024-10-15 DOI:10.3390/antibiotics13100973

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

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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 Escherichia coli carrying the tetA gene. We have screened guanethidine, a compound from the Chinese pharmacopoeia, which effectively potentiates the activity of tetracyclines by reversing resistance in tetA-positive Escherichia coli, 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.

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胍基恢复携带 tetA 基因的耐多药大肠杆菌对四环素的敏感性

病原菌的抗生素耐药性问题令人担忧，而新型治疗药物的匮乏又加剧了这一问题。抗生素佐剂在解决这一问题方面具有成本效益和高效性，因此是一种很有前景的解决方案，如β-内酰胺酶抑制剂舒巴坦（β-内酰胺类佐剂）和二氢叶酸还原酶抑制剂三甲氧苄啶（磺胺类佐剂）。本研究旨在从以前批准的药物清单中发现四环素类药物的潜在佐剂，以恢复携带 tetA 基因的大肠杆菌对四环素类药物的敏感性。我们从中国药典中筛选出一种化合物胍乙啶，它能有效增强四环素类药物的活性，逆转 tetA 阳性大肠杆菌的抗药性，增强其抗菌效力，延缓抗药性的产生。胍乙啶通过抑制 TetA 外排泵发挥作用，从而提高四环素类药物的细胞内浓度。我们的研究结果表明，胍乙啶有望成为一种抗生素辅助剂。

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来源期刊

Antibiotics-Basel Pharmacology, Toxicology and Pharmaceutics-General Pharmacology, Toxicology and Pharmaceutics

CiteScore

7.30

自引率

14.60%

发文量

1547

审稿时长

11 weeks

期刊介绍： Antibiotics (ISSN 2079-6382) is an open access, peer reviewed journal on all aspects of antibiotics. Antibiotics is a multi-disciplinary journal encompassing the general fields of biochemistry, chemistry, genetics, microbiology and pharmacology. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. Therefore, there is no restriction on the length of papers.