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The impact of drug resistance on Mycobacterium tuberculosis physiology: what can we learn from rifampicin?耐药性对结核分枝杆菌生理学的影响：从利福平我们能学到什么？
Emerg Microbes Infect. 2014 Mar;3(3):e17. doi: 10.1038/emi.2014.17. Epub 2014 Mar 12.
2
Tuberculosis, drug resistance, and the history of modern medicine.结核病、耐药性与现代医学史
N Engl J Med. 2012 Sep 6;367(10):931-6. doi: 10.1056/NEJMra1205429.
3
Analysis of gene mutations associated with isoniazid, rifampicin and ethambutol resistance among Mycobacterium tuberculosis isolates from Ethiopia.分析来自埃塞俄比亚的结核分枝杆菌分离株中与异烟肼、利福平及乙胺丁醇耐药相关的基因突变。
BMC Infect Dis. 2012 Feb 10;12:37. doi: 10.1186/1471-2334-12-37.
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Clinical failures associated with rpoB mutations in phenotypically occult multidrug-resistant Mycobacterium tuberculosis.与表型隐匿性耐多药结核分枝杆菌 rpoB 突变相关的临床失败。
Int J Tuberc Lung Dis. 2012 Feb;16(2):216-20. doi: 10.5588/ijtld.11.0178.
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Isoniazid and rifampicin resistance-associated mutations in Mycobacterium tuberculosis isolates from Yangon, Myanmar: implications for rapid molecular testing.缅甸仰光结核分枝杆菌分离株中异烟肼和利福平耐药相关突变：对快速分子检测的意义
J Antimicrob Chemother. 2009 Oct;64(4):694-701. doi: 10.1093/jac/dkp292. Epub 2009 Aug 26.
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Molecular characterization of drug-resistant Mycobacterium tuberculosis isolates in Guangdong, China.中国广东耐药结核分枝杆菌分离株的分子特征
Jpn J Infect Dis. 2009 Jul;62(4):270-4.
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Mutations in rpoB and katG genes in Mycobacterium isolates from the Southeast of Mexico.来自墨西哥东南部的分枝杆菌分离株中rpoB和katG基因的突变。
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Rate and amplification of drug resistance among previously-treated patients with tuberculosis in Kampala, Uganda.乌干达坎帕拉既往接受过治疗的结核病患者的耐药率及耐药性增强情况。
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Rapid molecular detection of rifampicin resistance facilitates early diagnosis and treatment of multi-drug resistant tuberculosis: case control study.利福平耐药性的快速分子检测有助于多药耐药结核病的早期诊断和治疗：病例对照研究
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结核分枝杆菌分离株中与利福平及异烟肼耐药相关的rpoB和katG基因突变的基因型检测：马来西亚吉兰丹州的本地情况

Genotypic Detection of rpoB and katG Gene Mutations Associated with Rifampicin and Isoniazid Resistance in Mycobacterium Tuberculosis Isolates: A Local Scenario (Kelantan).

作者信息

Ismail Nurul-Ain, Ismail Mohd Fazli, Noor Siti Suraiya Md, Camalxaman Siti Nazrina

机构信息

Department of Medical Laboratory Technology, Faculty of Health Sciences, Universiti Teknologi MARA, 42300, Bandar Puncak Alam, Selangor, Malaysia.

Department of Medical Microbiology and Parasitology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia.

出版信息

Malays J Med Sci. 2016 Jan;23(1):22-6.

PMID:27540322
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4975585/
Abstract

BACKGROUND

Drug resistant tuberculosis (DR-TB) remains a public health issue that is of major concern on a global scale. The characterisation of clinical isolates may provide key information regarding the underlying mechanisms of drug resistance, and helps to augment therapeutic options. This study aims to evaluate the frequency of gene mutations associated with Rifampicin (RIF) and Isoniazid (INH) resistance among nine clinical isolates.

METHODS

A total of nine drug resistant Mycobacterium tuberculosis clinical isolates were screened for genetic mutations in rpoB and katusing polymerase chain reaction (PCR) amplification and DNA sequencing. Genotypic analysis was performed to detect the mutations in the sequence of the target genes.

RESULTS

Our findings reveal that 80% of the isolates possess mutations at codon 119 (His119Tyr) and 135 (Arg135Trp and Ser135Leu) within the rpoB gene; and 70% possess mutations in the katG gene at codon 238 with amino acid change (Leu238Arg).

CONCLUSION

Findings from this study provide an overview of the current situation of RIF and INH resistance in a hospital Universiti Sains Malaysia (HUSM) located in Kelantan, Malaysia, which could facilitate molecular-based detection methods of drug-resistant strains. Further information regarding the molecular mechanisms involved in resistance in RR-/MDR-TB should be addressed in the near future.

摘要

背景

耐多药结核病（DR-TB）仍是一个在全球范围内备受关注的公共卫生问题。临床分离株的特征分析可为耐药潜在机制提供关键信息，并有助于增加治疗选择。本研究旨在评估9株临床分离株中与利福平（RIF）和异烟肼（INH）耐药相关的基因突变频率。

方法

采用聚合酶链反应（PCR）扩增和DNA测序技术，对9株耐多药结核分枝杆菌临床分离株的rpoB和katG基因进行基因突变筛查。进行基因分型分析以检测目标基因序列中的突变。

结果

我们的研究结果显示，80%的分离株在rpoB基因的第119密码子（His119Tyr）和第135密码子（Arg135Trp和Ser135Leu）处存在突变；70%的分离株在katG基因的第238密码子处存在氨基酸改变（Leu238Arg）的突变。

结论

本研究结果概述了马来西亚吉兰丹州马来西亚理科大学医院（HUSM）利福平和异烟肼耐药的现状，这有助于基于分子的耐药菌株检测方法。关于RR-/MDR-TB耐药相关分子机制的更多信息应在不久的将来得到解决。