外源性 NADH 可促进氨基糖苷类抗生素对arda Edwardsiella 的杀菌作用。

IF 5.5 1区 农林科学 Q1 IMMUNOLOGY
Virulence Pub Date : 2024-12-01 Epub Date: 2024-06-17 DOI:10.1080/21505594.2024.2367647
Yilin Zhong, Juan Guo, Ziyi Zhang, Yu Zheng, Manjun Yang, Yubin Su
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引用次数: 0

摘要

由于滥用和过度使用抗生素,全球耐多药细菌激增,给人类和动物健康带来巨大风险。随着现有抗生素逐渐失去效用,而新抗生素的开发又旷日持久,因此迫切需要替代品来遏制疾病的传播。值得注意的是,通过使用非抗生素物质来改善抗生素的杀菌效果已成为一种可行的策略。尽管还原型烟酰胺腺嘌呤二核苷酸(NADH)可能在调节细菌耐药性方面起着至关重要的作用,但有关外源给药后代谢概况和细菌耐药性如何变化的研究却很少。因此,本研究旨在利用代谢组学阐明对多种抗生素具有耐药性的塔尔达爱德华氏菌(E. tarda)在外源性添加 NADH 后发生的代谢变化。研究了这些变化对新霉素杀菌活性的影响。NADH 增强了氨基糖苷类抗生素对 E. tarda ATCC15947 的效力,在低剂量时就能达到根除细菌的目的。代谢组学分析表明,NADH 通过促进嘌呤代谢和能量代谢,提高了三磷酸腺苷(ATP)水平,从而重新规划了 ATCC15947 的代谢概况。ATP 水平的提高在增强新霉素的杀菌作用方面发挥了关键作用。此外,外源性 NADH 还能促进四环素类和氯霉素的杀菌效果。NADH 与新霉素联用对其他临床耐药细菌也有效,包括嗜水气单胞菌、副溶血性弧菌、耐甲氧西林金黄色葡萄球菌和单增李斯特菌。这些结果可能有助于开发有效的方法,预防和管理水产养殖和临床环境中由 E. tarda 引起的感染和多重耐药性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Exogenous NADH promotes the bactericidal effect of aminoglycoside antibiotics against Edwardsiella tarda.

The global surge in multidrug-resistant bacteria owing to antibiotic misuse and overuse poses considerable risks to human and animal health. With existing antibiotics losing their effectiveness and the protracted process of developing new antibiotics, urgent alternatives are imperative to curb disease spread. Notably, improving the bactericidal effect of antibiotics by using non-antibiotic substances has emerged as a viable strategy. Although reduced nicotinamide adenine dinucleotide (NADH) may play a crucial role in regulating bacterial resistance, studies examining how the change of metabolic profile and bacterial resistance following by exogenous administration are scarce. Therefore, this study aimed to elucidate the metabolic changes that occur in Edwardsiella tarda (E. tarda), which exhibits resistance to various antibiotics, following the exogenous addition of NADH using metabolomics. The effects of these alterations on the bactericidal activity of neomycin were investigated. NADH enhanced the effectiveness of aminoglycoside antibiotics against E. tarda ATCC15947, achieving bacterial eradication at low doses. Metabolomic analysis revealed that NADH reprogrammed the ATCC15947 metabolic profile by promoting purine metabolism and energy metabolism, yielding increased adenosine triphosphate (ATP) levels. Increased ATP levels played a crucial role in enhancing the bactericidal effects of neomycin. Moreover, exogenous NADH promoted the bactericidal efficacy of tetracyclines and chloramphenicols. NADH in combination with neomycin was effective against other clinically resistant bacteria, including Aeromonas hydrophila, Vibrio parahaemolyticus, methicillin-resistant Staphylococcus aureus, and Listeria monocytogenes. These results may facilitate the development of effective approaches for preventing and managing E. tarda-induced infections and multidrug resistance in aquaculture and clinical settings.

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来源期刊
Virulence
Virulence IMMUNOLOGY-MICROBIOLOGY
CiteScore
9.20
自引率
1.90%
发文量
123
审稿时长
6-12 weeks
期刊介绍: Virulence is a fully open access peer-reviewed journal. All articles will (if accepted) be available for anyone to read anywhere, at any time immediately on publication. Virulence is the first international peer-reviewed journal of its kind to focus exclusively on microbial pathogenicity, the infection process and host-pathogen interactions. To address the new infectious challenges, emerging infectious agents and antimicrobial resistance, there is a clear need for interdisciplinary research.
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