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New mutation sites associated with isoniazid resistance in Mycobacterium tuberculosis and their application

A technology for Mycobacterium tuberculosis and drug-resistant mutations, applied in the direction of microbial-based methods, microbial measurement/inspection, biochemical equipment and methods, etc., can solve the problems of increasing the chance of spreading drug-resistant strains, taking a long time, and affecting patient diagnosis and treatment, etc. problems, to achieve the effect of improving molecular detection level, shortening diagnosis time, saving treatment time and cost

Inactive Publication Date: 2017-07-11
广东省结核病控制中心
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AI Technical Summary

Problems solved by technology

These methods mainly use typical mutations such as katG, inhA, ahpC, and kasA to detect whether the same mutation occurs in Mycobacterium tuberculosis in the sample, so as to quickly determine whether Mycobacterium tuberculosis is resistant to isoniazid, but there are still many isoniazid-resistant bacteria. Mycobacterium tuberculosis with nicotinic acid could not be detected, false negative
[0005] The high drug resistance rate of tuberculosis is an important reason for the difficulty of controlling the tuberculosis epidemic. However, the traditional drug susceptibility test of Mycobacterium tuberculosis takes a long time, affects the diagnosis and treatment of patients, and increases the chance of drug-resistant strains spreading. Therefore, the rapid identification of tuberculosis by molecular biological methods can be effectively improved. The detection rate and accuracy of mycobacterial resistance are of great significance

Method used

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  • New mutation sites associated with isoniazid resistance in Mycobacterium tuberculosis and their application
  • New mutation sites associated with isoniazid resistance in Mycobacterium tuberculosis and their application
  • New mutation sites associated with isoniazid resistance in Mycobacterium tuberculosis and their application

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Embodiment 1

[0024] 1. Prediction of base mutation sites associated with INH drug resistance

[0025] First, using deep-sequencing technology, the whole genome of 161 strains of Mycobacterium tuberculosis from China was sequenced, including 44 strains of sensitive strains, 94 strains of multidrug-resistant strains (MDR), and 23 strains of extensively drug-resistant strains (XDR). The H37Rv standard Mycobacterium tuberculosis strain genome sequence was used as a control for bioinformatics analysis, and a batch of new genes closely related to drug resistance and single nucleotide polymorphism (SNP) sites in the intergenic region (IGR) were found, among which The single-base mutation site in the intergenic region Rv1482c-Rv1483* has a high correlation with isoniazid (INH) resistance, and its P value is 0, as shown in Table 1.

[0026] Table 1 Correlation between single-base mutation sites in the intergenic region FABG1 and different drug resistances

[0027] drug resistance spectrum...

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Abstract

The invention discloses a new mutation site related to isoniazide resistance of mycobacterium tuberculosis and an application thereof. The new mutation site is positioned at a 1673425th site of a standard strain H37Rv genome, that is a 126th base in an intergenic region of Rv1482c to Rv1483*, and the generated point mutation comprises that a base C is mutated into a base T or a base A. The found new mutation site can be used as a detection target applied in detection of the isoniazide resistance of mycobacterium tuberculosis, improves the molecular detection level of the isoniazide resistance of mycobacterium tuberculosis, shortens the diagnosis time of patients, and saves the treating time and cost for the patients. The mycobacterium tuberculosis drug-resistant mutation site is explained to possibly occur in a non-coding region, the base mutation of the intergenic region is prompted to be possibly related to the drug resistance, and a drug-resistant biomarker also exists. The invention provides a new idea for finding out a new and more effective mycobacterium tuberculosis drug-resistant molecular marker.

Description

technical field [0001] The invention relates to high-throughput screening and verification of drug-resistant base mutation sites of Mycobacterium tuberculosis, in particular to the screening and verification of isoniazid drug-resistant mutation sites of Mycobacterium tuberculosis. Background technique [0002] Tuberculosis is a chronic infectious disease caused by Mycobacterium tuberculosis infection. Mycobacterium tuberculosis may invade various organs of the human body, but mainly invades the lungs, which is called pulmonary tuberculosis. By the late 1980s, due to factors such as poverty, AIDS, population mobility, and drug resistance, the incidence and mortality of tuberculosis rose rapidly around the world, becoming the most serious infectious disease in the world alongside AIDS. The drug resistance of Mycobacterium tuberculosis is serious, and the drug resistance rate is as high as 46%, which poses a severe challenge to the prevention and treatment of tuberculosis. ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12N15/11C12Q1/68C12R1/32
Inventor 陈涛钟球周琳陈亮毕利军郭卉欣李海成陈瑜晖蒋莉尹建军廖庆华舒杨王威
Owner 广东省结核病控制中心
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