MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
Risk Assessment Center of Veterinary Drug Residue and Antimicrobial Resistance, Nanjing Agricultural University, Nanjing, China.
Antimicrob Agents Chemother. 2023 Jul 18;67(7):e0004723. doi: 10.1128/aac.00047-23. Epub 2023 Jun 8.
The emergence of TMexCD1-TOprJ1, a novel transferable resistance-nodulation-division (RND)-type efflux pump conferring resistance to tigecycline, is now a serious public health issue in the world. Here, we found that melatonin synergistically enhanced the antibacterial efficacy of tigecycline against -positive Klebsiella pneumoniae by disrupting the proton driving force and efflux function to promote the accumulation of tigecycline into cells, damaging cell membrane integrity and causing the leakage of cell contents. The synergistic effect was further validated by a murine thigh infection model. The results revealed that the melatonin/tigecycline combination is a potential therapy to combat resistant bacteria carrying the gene.
TMexCD1-TOprJ1 的出现是一个新的可转移的耐药性结节分裂（RND）型外排泵，它赋予了对替加环素的耐药性，现在是世界范围内一个严重的公共卫生问题。在这里，我们发现褪黑素通过破坏质子驱动力和外排功能，促进替加环素进入细胞积累，破坏细胞膜完整性并导致细胞内容物泄漏，从而协同增强了替加环素对阳性克雷伯氏肺炎菌的抗菌作用。协同作用进一步通过小鼠大腿感染模型得到验证。结果表明，褪黑素/替加环素联合用药是一种对抗携带 基因的耐药菌的潜在疗法。
