A Potential Nontraditional Approach To Combat tmexCD1-toprJ1-Mediated Tigecycline Resistance: Melatonin as a Synergistic Adjuvant of Tigecycline
A Potential Nontraditional Approach To Combat tmexCD1-toprJ1-Mediated Tigecycline Resistance: Melatonin as a Synergistic Adjuvant of Tigecycline
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DOI：
10.1128/aac.00047-23
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发表时间：
2023-06
影响因子：
4.9
通讯作者：
Xiaoming Wang;Ting Liu;Xi Lv;Naiyan Sun;Fan Li;L. Luo;Xiangkai Zhuge;Jinhu Huang;Liping Wang
中科院分区：
文献类型：
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作者：
Xiaoming Wang;Ting Liu;Xi Lv;Naiyan Sun;Fan Li;L. Luo;Xiangkai Zhuge;Jinhu Huang;Liping Wang
TMexCD 1-TOprJ 1是一种新型的可转移的耐药-增殖-分裂（RND）型外排泵，可引起替加环素的耐药，是目前世界范围内一个严重的公共卫生问题。在这里，我们发现褪黑激素协同增强替加环素对tmexCD 1-toprJ 1阳性肺炎克雷伯菌的抗菌功效，通过破坏质子驱动力和外排功能促进替加环素在细胞中的积累，破坏细胞膜的完整性并导致细胞内容物的泄漏。摘要TMexCD 1-TOprJ 1是一种新型的耐药细胞外排泵，它的出现使替加环素耐药成为一个严重的公共卫生问题。在这里，我们发现褪黑激素协同增强替加环素对tmexCD 1-toprJ 1阳性肺炎克雷伯菌的抗菌功效，通过破坏质子驱动力和外排功能促进替加环素在细胞中的积累，破坏细胞膜的完整性并导致细胞内容物的泄漏。通过鼠大腿感染模型进一步验证了协同效应。结果表明，褪黑激素/替加环素组合是一种潜在的治疗方法，可以对抗携带tmexCD 1-toprJ 1基因的耐药细菌。
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 tmexCD1-toprJ1-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. ABSTRACT 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 tmexCD1-toprJ1-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 tmexCD1-toprJ1 gene.