Guo Fang, Shi Chunfeng, Huang Li, Yao Yizhou, Qiao Liping, Zhu Dekang, Wang Mingshu, Jia Renyong, Chen Shun, Zhao Xinxin, Wu Ying, Zhang Shaqiu, Zhang Ling, Yu Yanling, Götz Friedrich, Cheng Anchun, Liu Mafeng
Engineering Research Center of Southwest Animal Disease Prevention and Control Technology, Ministry of Education of the People's Republic of China, Chengdu 611130, PR China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu 611130, PR China; International Joint Research Center for Animal Disease Prevention and Control of Sichuan Province, Chengdu 611130, PR China; Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, PR China.
Microbial Genetics, Interfaculty Institute of Microbiology and Infection Medicine Tübingen (IMIT), University of Tübingen, Tübingen 72076, Germany.
Poult Sci. 2025 Jul 3;104(10):105513. doi: 10.1016/j.psj.2025.105513.
The rapid emergence of antibiotic-resistant bacteria has become a global concern. In particular, the overuse of antibiotics in the breeding industry has accelerated the emergence of antibiotic-resistant bacteria, but the mechanisms driving this phenomenon are not fully understood. Here, using the multidrug-resistant bacterium R. anatipestifer as a proof of concept, we show that the chaperone DnaK promoted the emergence and accumulation of antibiotic-resistant clones. Compared to the ∆dnaK, the wild type produced more resistant clones under antibiotic stress and accelerated the accumulation of resistance mutations under the second antibiotic stress. Importantly, it was indicated that the broad DnaK molecular chaperone inhibitor, telaprevir (TP), effectively decreases the frequency of antibiotics resistant (FOR) in R. anatipestifer through inhibiting the ATPase activation of the DnaK molecular chaperone. Taken together, this study suggested that the chaperone DnaK can be used as a target for drug design to control the emergence and accumulation of antibiotic-resistant clones in R. anatipestifer and reduce the risk of antibiotic resistance in clinical treatment.
抗生素耐药细菌的迅速出现已成为全球关注的问题。特别是，养殖业中抗生素的过度使用加速了抗生素耐药细菌的出现，但驱动这一现象的机制尚未完全了解。在这里，我们以多重耐药细菌鸭疫里默氏菌作为概念验证，表明伴侣蛋白DnaK促进了抗生素耐药克隆的出现和积累。与ΔdnaK相比，野生型在抗生素胁迫下产生了更多的耐药克隆，并在第二次抗生素胁迫下加速了耐药突变的积累。重要的是，研究表明，广泛的DnaK分子伴侣抑制剂替拉瑞韦（TP）通过抑制DnaK分子伴侣的ATP酶激活，有效降低了鸭疫里默氏菌的抗生素耐药频率（FOR）。综上所述，本研究表明，伴侣蛋白DnaK可作为药物设计的靶点，以控制鸭疫里默氏菌中抗生素耐药克隆的出现和积累，并降低临床治疗中抗生素耐药的风险。
