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

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

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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.

Tianqi Xu、Dan Fang、Fulei Li、Zhiqiang Wang、Yuan Liu

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Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses,College of Veterinary Medicine,Yangzhou University,Yangzhou 225009,China

Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses,College of Veterinary Medicine,Yangzhou University,Yangzhou 225009,China

Joint International Research Laboratory of Agriculture and Agri-Product Safety,the Ministry of Education of China,Yangzhou University,Yangzhou 225009,China

Institute of Comparative Medicine,Yangzhou University,Yangzhou 225009,China

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2024

10.34133/research.0245

研究(英文)

研究(英文)

CSTPCD
ISSN：
年,卷(期)：2024.2024(3)