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

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 ac...

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Autores principales: Li, Xue-Song, Xue, Jun-Ze, Qi, Yu, Muhammad, Inam, Wang, Hao, Li, Xuan-Yu, Luo, Yi-Jia, Zhu, Dao-Mi, Gao, Yun-Hang, Kong, Ling-Cong, Ma, Hong-Xia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10219361/
https://www.ncbi.nlm.nih.gov/pubmed/37240435
http://dx.doi.org/10.3390/ijms24109089
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author Li, Xue-Song
Xue, Jun-Ze
Qi, Yu
Muhammad, Inam
Wang, Hao
Li, Xuan-Yu
Luo, Yi-Jia
Zhu, Dao-Mi
Gao, Yun-Hang
Kong, Ling-Cong
Ma, Hong-Xia
author_facet Li, Xue-Song
Xue, Jun-Ze
Qi, Yu
Muhammad, Inam
Wang, Hao
Li, Xuan-Yu
Luo, Yi-Jia
Zhu, Dao-Mi
Gao, Yun-Hang
Kong, Ling-Cong
Ma, Hong-Xia
author_sort Li, Xue-Song
collection PubMed
description 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.
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spelling pubmed-102193612023-05-27 Citric Acid Confers Broad Antibiotic Tolerance through Alteration of Bacterial Metabolism and Oxidative Stress Li, Xue-Song Xue, Jun-Ze Qi, Yu Muhammad, Inam Wang, Hao Li, Xuan-Yu Luo, Yi-Jia Zhu, Dao-Mi Gao, Yun-Hang Kong, Ling-Cong Ma, Hong-Xia Int J Mol Sci Article 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. MDPI 2023-05-22 /pmc/articles/PMC10219361/ /pubmed/37240435 http://dx.doi.org/10.3390/ijms24109089 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Li, Xue-Song
Xue, Jun-Ze
Qi, Yu
Muhammad, Inam
Wang, Hao
Li, Xuan-Yu
Luo, Yi-Jia
Zhu, Dao-Mi
Gao, Yun-Hang
Kong, Ling-Cong
Ma, Hong-Xia
Citric Acid Confers Broad Antibiotic Tolerance through Alteration of Bacterial Metabolism and Oxidative Stress
title Citric Acid Confers Broad Antibiotic Tolerance through Alteration of Bacterial Metabolism and Oxidative Stress
title_full Citric Acid Confers Broad Antibiotic Tolerance through Alteration of Bacterial Metabolism and Oxidative Stress
title_fullStr Citric Acid Confers Broad Antibiotic Tolerance through Alteration of Bacterial Metabolism and Oxidative Stress
title_full_unstemmed Citric Acid Confers Broad Antibiotic Tolerance through Alteration of Bacterial Metabolism and Oxidative Stress
title_short Citric Acid Confers Broad Antibiotic Tolerance through Alteration of Bacterial Metabolism and Oxidative Stress
title_sort citric acid confers broad antibiotic tolerance through alteration of bacterial metabolism and oxidative stress
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10219361/
https://www.ncbi.nlm.nih.gov/pubmed/37240435
http://dx.doi.org/10.3390/ijms24109089
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