Inappropriate use of antibiotic enhances antibiotic resistance dissemination in ESBL-EC: Role of ydcz in outer membrane vesicles biogenesis and protein transport

IF 6.1 1区生物学 Q1 MICROBIOLOGY

Microbiological research Pub Date : 2024-05-31 DOI:10.1016/j.micres.2024.127774

Jinpeng Li , Chao Li , Chang Tan , Heting Xu , Yun Han , Yulian Hu , Jian Yang , Yizhi Tang , Changwei Lei , Hongning Wang

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引用次数: 0

Abstract

Extended-spectrumβ-lactam producing Escherichia coli (ESBL-EC) readily colonizes live poultry and serves as a major source of contamination in retail chicken meat, posing significant threats to public health. This study aims to investigate the impact of inappropriate antibiotic use on the dissemination and exacerbation of antibiotic resistance in ESBL-EC and explore the underlying molecular mechanisms. Through experimental analysis, we propose a hypothesis that inappropriate antibiotic use may exacerbate resistance by affecting vesicle formation and protein secretion. Experimental results demonstrate that under the influence of amoxicillin, the concentration of proteins secreted in outer membrane vehicles (OMVs) by ESBL-EC significantly increases, along with a significant upregulation in the expression of the CTX-M-55-type Extended-spectrum beta-lactamase (CTX-M-55). Proteomic analysis and differential gene knockout experiments identified the key protein YdcZ, associated with OMVs formation and protein transportation in ESBL-EC under amoxicillin treatment. Further investigations reveal direct interactions between YdcZ and other proteins (YdiH and BssR). Upon ydcz gene knockout, a significant decrease in protein concentration within OMVs is observed, accompanied by a noticeable reduction in protection against sensitive bacteria. These findings suggest a critical role of YdcZ in regulating the process of protein transportation to OMVs in ESBL-EC under the influence of amoxicillin. In summary, our research uncovers the significant role of inappropriate antibiotic use in promoting the secretion of OMVs by ESBL-EC, aiding the survival of antibiotic-sensitive bacteria in the vicinity of infection sites. These findings provide new insights into the mechanisms underlying antibiotic-induced bacterial resistance dissemination and offer novel avenues for exploring prevention and control strategies against bacterial resistance propagation.

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抗生素的不当使用会增强 ESBL-EC 的抗生素耐药性传播：ydcz在外膜囊泡生物生成和蛋白质转运中的作用

产生广谱β-内酰胺类药物的大肠埃希菌（ESBL-EC）很容易在活家禽中定植，是零售鸡肉的主要污染源，对公众健康构成严重威胁。本研究旨在调查抗生素使用不当对 ESBL-EC 抗生素耐药性传播和加剧的影响，并探索其潜在的分子机制。通过实验分析，我们提出了一个假设：抗生素的不当使用可能会通过影响囊泡的形成和蛋白质的分泌而加剧耐药性。实验结果表明，在阿莫西林的影响下，ESBL-EC在外膜载体（OMV）中分泌的蛋白质浓度显著增加，同时 CTX-M-55 型广谱 beta-内酰胺酶（CTX-M-55）的表达也显著上调。蛋白质组分析和差异基因敲除实验发现了关键蛋白 YdcZ，它与阿莫西林处理下 ESBL-EC 中 OMV 的形成和蛋白质运输有关。进一步的研究发现了 YdcZ 与其他蛋白（YdiH 和 BssR）之间的直接相互作用。在敲除ydcz基因后，观察到OMVs内的蛋白质浓度显著下降，同时对敏感细菌的保护能力也明显下降。这些发现表明，在阿莫西林的影响下，YdcZ 在调节 ESBL-EC 蛋白向 OMVs 转运的过程中起着关键作用。总之，我们的研究揭示了抗生素使用不当在促进 ESBL-EC 分泌 OMVs、帮助抗生素敏感细菌在感染部位附近存活方面的重要作用。这些发现为了解抗生素诱导细菌耐药性传播的机制提供了新的视角，并为探索预防和控制细菌耐药性传播的策略提供了新的途径。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Microbiological research 生物-微生物学

CiteScore

10.90

自引率

6.00%

发文量

249

审稿时长

29 days

期刊介绍： Microbiological Research is devoted to publishing reports on prokaryotic and eukaryotic microorganisms such as yeasts, fungi, bacteria, archaea, and protozoa. Research on interactions between pathogenic microorganisms and their environment or hosts are also covered.