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

Xiaoming Wang, Ting Liu, Xi Lv, Naiyan Sun, Fan Li, Lei Luo, Xiangkai Zhuge, Jinhu Huang, Liping Wang

2023Antimicrobial Agents and Chemotherapy12 citationsDOIOpen Access PDF

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.

Topics & Concepts

TigecyclineEffluxKlebsiella pneumoniaeBiologyPharmacologyMicrobiologyAntibioticsBiochemistryEscherichia coliGeneAntibiotic Resistance in BacteriaAntibiotics Pharmacokinetics and EfficacyUrinary Tract Infections Management