A Potential Nontraditional Approach To Combat 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
Author Information
Xiaoming Wang: MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China. ORCID
Ting Liu: MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
Xi Lv: MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
Naiyan Sun: MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
Fan Li: MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
Lei Luo: College of Pharmaceutical Sciences, Southwest University, Chongqing, China.
Xiangkai Zhuge: Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, China. ORCID
Jinhu Huang: MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China. ORCID
Liping Wang: MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China. ORCID
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 murinethigh infection model. The results revealed that the melatonin/Tigecycline combination is a potential therapy to combat resistant bacteria carrying the gene.
