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136个整合子耐药基因的概况及耐药水平

Profile and resistance levels of 136 integron resistance genes.

作者信息

Hipólito Alberto, García-Pastor Lucía, Vergara Ester, Jové Thomas, Escudero José Antonio

机构信息

Molecular Basis of Adaptation. Departamento de Sanidad Animal. Facultad de Veterinaria de la Universidad Complutense de Madrid, Madrid, Spain.

VISAVET Health Surveillance Centre, Universidad Complutense de Madrid, Madrid, Spain.

出版信息

NPJ Antimicrob Resist. 2023 Oct 11;1(1):13. doi: 10.1038/s44259-023-00014-3.

DOI:10.1038/s44259-023-00014-3
PMID:39843947
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11721406/
Abstract

Integrons have played a major role in the rise and spread of multidrug resistance in Gram-negative pathogens and are nowadays commonplace among clinical isolates. These platforms capture, stockpile, and modulate the expression of more than 170 antimicrobial resistance cassettes (ARCs) against most clinically-relevant antibiotics. Despite their importance, our knowledge on their profile and resistance levels is patchy, because data is scattered in the literature, often reported in different genetic backgrounds and sometimes extrapolated from sequence similarity alone. Here we have generated a collection of 136 ARCs against 8 antibiotic families and disinfectants. Cassettes are cloned in a vector designed to mimic the genetic environment of a class 1 integron, and transformed in Escherichia coli. We have measured the minimal inhibitory concentration (MIC) to the most relevant molecules from each antibiotic family. With more than 500 MIC values, we provide an exhaustive and comparable quantitation of resistance conferred by ARCs. Our data confirm known resistance trends and profiles while revealing important differences among closely related genes. We have also detected genes that do not confer the expected resistance, to the point of challenging the role of the whole family of qac genes in resistance against disinfectants. Our work provides a detailed characterization of integron resistance genes at-a-glance.

摘要

整合子在革兰氏阴性病原菌多重耐药性的产生和传播中发挥了重要作用,如今在临床分离株中很常见。这些平台捕获、储存并调节针对大多数临床相关抗生素的170多种抗菌耐药盒(ARC)的表达。尽管它们很重要,但我们对其特征和耐药水平的了解并不完整,因为数据分散在文献中,通常在不同的遗传背景下报道,有时仅从序列相似性推断而来。在这里,我们针对8个抗生素家族和消毒剂生成了136个ARC的集合。这些盒被克隆到一个设计用于模拟1类整合子遗传环境的载体中,并转化到大肠杆菌中。我们测量了对每个抗生素家族最相关分子的最低抑菌浓度(MIC)。通过500多个MIC值,我们提供了ARC赋予的耐药性的详尽且可比的定量分析。我们的数据证实了已知的耐药趋势和特征,同时揭示了密切相关基因之间的重要差异。我们还检测到了不赋予预期耐药性的基因,甚至对整个qac基因家族在抗消毒剂耐药性中的作用提出了质疑。我们的工作提供了整合子耐药基因的详细特征概述。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f527/11721406/ac4cba7f07a8/44259_2023_14_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f527/11721406/1edcf23ea489/44259_2023_14_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f527/11721406/0221c2b3b69e/44259_2023_14_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f527/11721406/d4f5f0405d09/44259_2023_14_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f527/11721406/a3a58e77d85e/44259_2023_14_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f527/11721406/ac4cba7f07a8/44259_2023_14_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f527/11721406/1edcf23ea489/44259_2023_14_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f527/11721406/3992fe1f8bf7/44259_2023_14_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f527/11721406/fd827f3453e3/44259_2023_14_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f527/11721406/426c40c5206f/44259_2023_14_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f527/11721406/0221c2b3b69e/44259_2023_14_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f527/11721406/d4f5f0405d09/44259_2023_14_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f527/11721406/a3a58e77d85e/44259_2023_14_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f527/11721406/ac4cba7f07a8/44259_2023_14_Fig8_HTML.jpg

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本文引用的文献

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Nucleic Acids Res. 2022 Aug 26;50(15):8566-8579. doi: 10.1093/nar/gkac662.
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IntegronFinder 2.0: Identification and Analysis of Integrons across Bacteria, with a Focus on Antibiotic Resistance in Klebsiella.整合子查找器2.0:细菌中整合子的鉴定与分析,重点关注克雷伯菌属中的抗生素耐药性
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Unbridled Integrons: A Matter of Host Factors.
染色体整合子是基因组中遗传和功能上分离的单位。
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Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis.2019 年全球细菌对抗菌药物耐药性的负担:系统分析。
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Non-clinical settings - the understudied facet of antimicrobial drug resistance.非临床环境——抗菌药物耐药性研究不足的方面。
Environ Microbiol. 2021 Dec;23(12):7271-7274. doi: 10.1111/1462-2920.15841. Epub 2021 Nov 13.
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