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韩国分离出的抗结核药物耐药性的分子分析

Molecular Analysis of Anti-Tuberculosis Drug Resistance of Isolated in the Republic of Korea.

作者信息

Jeon Se-Mi, Park Sanghee, Lim Na-Ra, Lee Noori, Jung Jihee, Sung Nackmoon, Kim Seonghan

机构信息

Division of Bacterial Disease Research, Korea National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju-si 28159, Republic of Korea.

Clinical Research Center, Masan National Tuberculosis Hospital, Changwon-si 51755, Republic of Korea.

出版信息

Antibiotics (Basel). 2023 Aug 17;12(8):1324. doi: 10.3390/antibiotics12081324.

Abstract

Rapid and accurate detection of tuberculosis (TB) drug resistance is critical for the successful treatment and control of TB. Here, we investigated resistance to anti-TB drugs and genetic variations in 215 drug-resistant isolates in Korea. Genetic variations were observed in Ser531Leu, Ser315Thr, and Asp94Gly; however, the minimum inhibitory concentrations varied, which can be attributed to other resistance mechanisms. Examination of genetic relatedness among drug-resistant isolates revealed that the cluster size of resistant bacteria was less than six strains, suggesting no evidence of a large-scale epidemic caused by a specific strain. However, mutants of the rifampicin-resistant isolates were composed of five types of clusters, suggesting that these compensatory mutations advance propagation. In the present study, more than 90% of the resistance mechanisms to major anti-TB drugs were identified, and the effect of each mutation on drug resistance was estimated. With the clinical application of recent next-generation sequencing-based susceptibility testing, the present study is expected to improve the clinical utilization of genotype-based drug susceptibility testing for the diagnosis and treatment of patients with drug-resistant TB.

摘要

快速准确地检测结核病(TB)耐药性对于结核病的成功治疗和控制至关重要。在此,我们调查了韩国215株耐药菌株对抗结核药物的耐药性及基因变异情况。在Ser531Leu、Ser315Thr和Asp94Gly中观察到基因变异;然而,最低抑菌浓度有所不同,这可能归因于其他耐药机制。对耐药菌株之间的基因相关性检查显示,耐药细菌的聚类大小小于6株,这表明没有证据表明存在由特定菌株引起的大规模流行。然而,耐利福平菌株的突变体由五种聚类类型组成,这表明这些补偿性突变促进了传播。在本研究中,确定了90%以上主要抗结核药物的耐药机制,并估计了每种突变对耐药性的影响。随着近期基于下一代测序的药敏试验在临床上的应用,本研究有望提高基于基因型的药敏试验在耐多药结核病患者诊断和治疗中的临床应用价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b265/10451913/4a9d9579455c/antibiotics-12-01324-g001.jpg

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