A Dietary Source of High Level of Fluoroquinolone Tolerance in mcr-Carrying Gram-Negative Bacteria  

作　　者：Tianqi Xu Dan Fang Fulei Li Zhiqiang Wang Yuan Liu 

机构地区：[1]Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses,College of Veterinary Medicine,Yangzhou University,Yangzhou 225009,China. [2]Joint International Research Laboratory of Agriculture and Agri-Product Safety,the Ministry of Education of China,Yangzhou University,Yangzhou 225009,China. [3]Institute of Comparative Medicine,Yangzhou University,Yangzhou 225009,China.

出　　处：《Research》2024年第3期105-121,共17页研究（英文）

基　　金：the National Key Research and Development Program of China(2021YFD1801000 and 2018YFA0903400);the National Natural Science Foundation of China(32222084,32172907,and 32002331);Jiangsu Agricultural Science and Technology Innovation Fund(CX(21)2010);a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD),and 111 Project D18007.

摘　　要：The emergence of antibiotic tolerance,characterized by the prolonged survival of bacteria following antibiotic exposure,in natural bacterial populations,especially in pathogens carrying antibiotic resistance genes,has been an increasing threat to public health.However,the major causes contributing to the formation of antibiotic tolerance and underlying molecular mechanisms are yet poorly understood.Herein,we show that potassium sorbate(PS),a widely used food additive,triggers a high level of fluoroquinolone tolerance in bacteria carrying mobile colistin resistance gene mcr.Mechanistic studies demonstrate that PS treatment results in the accumulation of intracellular fumarate,which activates bacterial two-component system and decreases the expression level of outer membrane protein OmpF,thereby reducing the uptake of ciprofloxacin.In addition,the supplementation of PS inhibits aerobic respiration,reduces reactive oxygen species production and alleviates DNA damage caused by bactericidal antibiotics.Furthermore,we demonstrate that succinate,an intermediate product of the tricarboxylic acid cycle,overcomes PS-mediated ciprofloxacin tolerance.In multiple animal models,ciprofloxacin treatment displays failure outcomes in PS preadministrated animals,including comparable survival and bacterial loads with the vehicle group.Taken together,our works offer novel mechanistic insights into the development of antibiotic tolerance and uncover potential risks associated with PS use.

关 键 词：OVERCOME thereby ADDITIVE 

分 类 号：R978.1[医药卫生—药品]