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Citric Acid Confers Broad Antibiotic Tolerance through Alteration of Bacterial Metabolism and Oxidative Stress

Authors :
Xue-Song Li
Jun-Ze Xue
Yu Qi
Inam Muhammad
Hao Wang
Xuan-Yu Li
Yi-Jia Luo
Dao-Mi Zhu
Yun-Hang Gao
Ling-Cong Kong
Hong-Xia Ma
Source :
International Journal of Molecular Sciences; Volume 24; Issue 10; Pages: 9089
Publication Year :
2023
Publisher :
Multidisciplinary Digital Publishing Institute, 2023.

Abstract

Antibiotic tolerance has become an increasingly serious crisis that has seriously threatened global public health. However, little is known about the exogenous factors that can trigger the development of antibiotic tolerance, both in vivo and in vitro. Herein, we found that the addition of citric acid, which is used in many fields, obviously weakened the bactericidal activity of antibiotics against various bacterial pathogens. This mechanistic study shows that citric acid activated the glyoxylate cycle by inhibiting ATP production in bacteria, reduced cell respiration levels, and inhibited the bacterial tricarboxylic acid cycle (TCA cycle). In addition, citric acid reduced the oxidative stress ability of bacteria, which led to an imbalance in the bacterial oxidation–antioxidant system. These effects together induced the bacteria to produce antibiotic tolerance. Surprisingly, the addition of succinic acid and xanthine could reverse the antibiotic tolerance induced by citric acid in vitro and in animal infection models. In conclusion, these findings provide new insights into the potential risks of citric acid usage and the relationship between antibiotic tolerance and bacterial metabolism.

Details

Language :
English
ISSN :
14220067
Database :
OpenAIRE
Journal :
International Journal of Molecular Sciences; Volume 24; Issue 10; Pages: 9089
Accession number :
edsair.doi.dedup.....7ff134e2ca3ef48df68d2a4ff14eb011
Full Text :
https://doi.org/10.3390/ijms24109089