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遗传决定因素与……中抗生素耐药表型的预测

Genetic Determinants and Prediction of Antibiotic Resistance Phenotypes in .

作者信息

Lauener Francis N, Imkamp Frank, Lehours Philippe, Buissonnière Alice, Benejat Lucie, Zbinden Reinhard, Keller Peter M, Wagner Karoline

机构信息

Institute of Medical Microbiology, University of Zurich, 8006 Zurich, Switzerland.

INSERM UMR1053, Bordeaux Research in Translational Oncology, BaRITOn, Université de Bordeaux, 33076 Bordeaux, France.

出版信息

J Clin Med. 2019 Jan 7;8(1):53. doi: 10.3390/jcm8010053.

DOI:10.3390/jcm8010053
PMID:30621024
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6351930/
Abstract

is a major human pathogen. Diagnosis of infection and determination of its antibiotic susceptibility still mainly rely on culture and phenotypic drug susceptibility testing (DST) that is time-consuming and laborious. Whole genome sequencing (WGS) has recently emerged in medical microbiology as a diagnostic tool for reliable drug resistance prediction in bacterial pathogens. The aim of this study was to compare phenotypic DST results with the predictions based on the presence of genetic determinants identified in the genome using WGS. Phenotypic resistance to clarithromycin, metronidazole, tetracycline, levofloxacin, and rifampicin was determined in 140 clinical isolates by E-Test, and the occurrence of certain single nucleotide polymorphisms (SNPs) in target genes was determined by WGS. Overall, there was a high congruence of >99% between phenotypic DST results for clarithromycin, levofloxacin, and rifampicin and SNPs identified in the 23S rRNA, , and gene. However, it was not possible to infer a resistance phenotype for metronidazole based on the occurrence of distinct SNPs in and . All 140 isolates analysed in this study were susceptible to tetracycline, which was in accordance with the absence of double or triple nucleotide substitutions in the 16S rRNA gene.

摘要

是一种主要的人类病原体。感染的诊断及其抗生素敏感性的确定仍然主要依赖于培养和表型药物敏感性测试(DST),这既耗时又费力。全基因组测序(WGS)最近在医学微生物学中作为一种用于细菌病原体可靠耐药性预测的诊断工具出现。本研究的目的是将表型DST结果与基于使用WGS在基因组中鉴定出的遗传决定因素的预测结果进行比较。通过E-Test测定了140株临床分离株对克拉霉素、甲硝唑、四环素、左氧氟沙星和利福平的表型耐药性,并通过WGS测定了靶基因中某些单核苷酸多态性(SNP)的发生情况。总体而言,克拉霉素、左氧氟沙星和利福平的表型DST结果与在23S rRNA、和基因中鉴定出的SNP之间的一致性高达99%以上。然而,根据和中不同SNP的发生情况无法推断甲硝唑的耐药表型。本研究分析的所有140株分离株对四环素均敏感,这与16S rRNA基因中不存在双核苷酸或三核苷酸取代一致。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac61/6351930/543f2313e06d/jcm-08-00053-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac61/6351930/543f2313e06d/jcm-08-00053-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac61/6351930/543f2313e06d/jcm-08-00053-g001.jpg

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