Alkaline arginine promotes the gentamicin-mediated killing of drug-resistant Salmonella by increasing NADH concentration and proton motive force

Frontiers in Microbiology

Microbiology

Chunyang Zhu¹  Heng Yang¹  Binghu Fang¹  Yanhong Zhou¹  Jian Kang²  Jinglin Lin² 

[1] Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, China;National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, China;School of Animal Science and Technology, Guangdong Polytechnic of Science and Trade, Guangzhou, China;

关键词: Salmonella;    arginine;    gentamicin;    resistance;    proton motive force;   

DOI  :  10.3389/fmicb.2023.1237825

 received in 2023-06-10, accepted in 2023-08-29,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionAntimicrobial resistance, especially the development of multidrug-resistant strains, is an urgent public health threat. Antibiotic adjuvants have been shown to improve the treatment of resistant bacterial infections.MethodsWe verified that exogenous L-arginine promoted the killing effect of gentamicin against Salmonella in vitro and in vivo, and measured intracellular ATP, NADH, and PMF of bacteria. Gene expression was determined using real-time quantitative PCR.ResultsThis study found that alkaline arginine significantly increased gentamicin, tobramycin, kanamycin, and apramycin-mediated killing of drug-resistant Salmonella, including multidrug-resistant strains. Mechanistic studies showed that exogenous arginine was shown to increase the proton motive force, increasing the uptake of gentamicin and ultimately inducing bacterial cell death. Furthermore, in mouse infection model, arginine effectively improved gentamicin activity against Salmonella typhimurium.DiscussionThese findings confirm that arginine is a highly effective and harmless aminoglycoside adjuvant and provide important evidence for its use in combination with antimicrobial agents to treat drug-resistant bacterial infections.

【 授权许可】

Unknown   
Copyright © 2023 Zhu, Zhou, Kang, Yang, Lin and Fang.