A Potential Nontraditional Approach To Combat tmexCD1-toprJ1- Mediated Tigecycline Resistance: Melatonin as a Synergistic Adjuvant of Tigecycline

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.