A Potential Nontraditional Approach To Combat tmexCD1-toprJ1- Mediated Tigecycline Resistance: Melatonin as a Synergistic Adjuvant of Tigecycline.
Xiaoming WangTing LiuXi LvNaiyan SunFan LiLei LuoXiangkai ZhugeJinhu HuangLiping WangPublished in: Antimicrobial agents and chemotherapy (2023)
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.
Keyphrases
- klebsiella pneumoniae
- multidrug resistant
- acinetobacter baumannii
- escherichia coli
- public health
- drug resistant
- single cell
- induced apoptosis
- early stage
- stem cells
- pseudomonas aeruginosa
- single molecule
- cell therapy
- cancer therapy
- genome wide
- drug delivery
- signaling pathway
- cell proliferation
- cell death
- essential oil
- replacement therapy
- genome wide analysis