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澳大利亚维多利亚州非伤寒沙门氏菌的抗菌药物耐药性的基因组多样性。

Genomic diversity of antimicrobial resistance in non-typhoidal in Victoria, Australia.

机构信息

Department of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.

Microbiological Diagnostic Unit Public Health Laboratory, Department of Microbiology & Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.

出版信息

Microb Genom. 2021 Dec;7(12). doi: 10.1099/mgen.0.000725.

Abstract

Non-typhoidal (NTS) is the second most common cause of foodborne bacterial gastroenteritis in Australia with antimicrobial resistance (AMR) increasing in recent years. Whole-genome sequencing (WGS) provides opportunities for detection of AMR determinants. The objectives of this study were two-fold: (1) establish the utility of WGS analyses for inferring phenotypic resistance in NTS, and (2) explore clinically relevant genotypic AMR profiles to third generation cephalosporins (3GC) in NTS lineages. The concordance of 2490 NTS isolates with matched WGS and phenotypic susceptibility data against 13 clinically relevant antimicrobials was explored. serovar prediction and typing was performed on assembled reads and interrogated for known AMR determinants. The surrounding genomic context, plasmid determinants and co-occurring AMR patterns were further investigated for multidrug resistant serovars harbouring , or . Our data demonstrated a high correlation between WGS and phenotypic susceptibility testing. Phenotypic-genotypic concordance was observed between 2440/2490 (98.0 %) isolates, with overall sensitivity and specificity rates >98 % and positive and negative predictive values >97 %. The most common AMR determinants were , , (A), and . Phenotypic resistance to cefotaxime and azithromycin was low and observed in 6.2 % (151/2486) and 0.9 % (16/1834) of the isolates, respectively. Several multi-drug resistant NTS lineages were resistant to 3GC due to different genetic mechanisms including , or . This study shows WGS can enhance existing AMR surveillance in NTS datasets routinely produced in public health laboratories to identify emerging AMR in NTS. These approaches will be critical for developing capacity to detect emerging public health threats such as resistance to 3GC.

摘要

非伤寒型(NTS)是澳大利亚第二大常见食源性病原体细菌肠胃炎的病原体,近年来其抗生素耐药性(AMR)不断增加。全基因组测序(WGS)为检测 AMR 决定因素提供了机会。本研究的目的有两个:(1)确定 WGS 分析在推断 NTS 表型耐药性方面的作用;(2)探索 NTS 谱系中第三代头孢菌素(3GC)的临床相关基因型 AMR 谱。研究探索了 2490 株与匹配的 WGS 和表型药敏数据相匹配的 NTS 分离株对 13 种临床相关抗菌药物的一致性。对组装后的读数进行血清型预测和分型,并对已知的 AMR 决定因素进行了检测。对携带 、 或 的多药耐药血清型进一步研究了其周围基因组环境、质粒决定因素和共存的 AMR 模式。我们的数据表明,WGS 与表型药敏试验之间具有高度相关性。2440/2490(98.0%)株之间观察到表型-基因型一致性,总体敏感性和特异性率>98%,阳性和阴性预测值>97%。最常见的 AMR 决定因素为 、 、 (A)、 和 。对头孢噻肟和阿奇霉素的表型耐药性较低,分别在 6.2%(151/2486)和 0.9%(16/1834)的分离株中观察到。由于不同的遗传机制,包括 、 或 ,几种多药耐药 NTS 谱系对 3GC 耐药。本研究表明,WGS 可以增强公共卫生实验室常规产生的 NTS 数据集的现有 AMR 监测,以识别 NTS 中的新出现的 AMR。这些方法对于检测新出现的公共卫生威胁(如对 3GC 的耐药性)的能力至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e694/8767345/e883341895e0/mgen-7-0725-g001.jpg

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