Fructose-enabled killing of antibiotic-resistant Salmonella enteritidis by gentamicin: Insight from reprogramming metabolomics

文献类型： 外文期刊

第一作者： Jiang, Ming

作者： Jiang, Ming;Xie, Chun-Lin;Chen, Peng;Luo, Wei;Lin, Chu-xiao;Shu, Ding-Ming;Luo, Cheng-long;Qu, Hao;Ji, Jian;Jiang, Ming;Li, Xia;Wang, Qiao;Qu, Hao;Ji, Jian

作者机构：

关键词： Salmonella enterica; Aminoglycoside antibiotics; Metabolomics; Antibiotic resistance; Chicken

期刊名称：INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS （ 影响因子：10.8； 五年影响因子：7.2 ）

ISSN： 0924-8579

年卷期： 2023 年 62 卷 3 期

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收录情况： SCI

摘要： Salmonella enterica is a food-borne pathogen that poses a severe threat to both poultry production and human health. Antibiotics are critical for the initial treatment of bacterial infections. However, the overuse and misuse of antibiotics results in the rapid evolution of antibiotic-resistant bacteria, and the discov-ery and development of new antibiotics are declining. Therefore, understanding antibiotic resistance mechanisms and developing novel control measures are essential. In the present study, GC-MS-based metabolomics analysis was performed to determine the metabolic profile of gentamicin sensitive (SE-S) and resistant (SE-R) S. enterica . Fructose was identified as a crucial biomarker. Further analysis demon-strated a global depressed central carbon metabolism and energy metabolism in SE-R. The decrease in the pyruvate cycle reduces the production of NADH and ATP, causing a decrease in membrane poten-tial, which contributes to gentamicin resistance. Exogenous fructose potentiated the effectiveness of gen-tamicin in killing SE-R by promoting the pyruvate cycle, NADH, ATP and membrane potential, thereby increasing gentamicin intake. Further, fructose plus gentamicin improved the survival rate of chicken in-fected with gentamicin-resistant Salmonella in vivo . Given that metabolite structures are conserved across species, fructose identified from bacteria could be used as a biomarker for breeding disease-resistant phenotypes in chicken. Therefore, a novel strategy is proposed for fighting against antibiotic-resistant S. enterica , including exploring molecules suppressed by antibiotics and providing a new approach to find pathogen targets for disease resistance in chicken breeding.& COPY; 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )

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