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俄罗斯 HIV 阳性和 HIV 阴性结核病患者中结核分枝杆菌耐药分离株的分子特征。

Molecular characteristics of Mycobacterium tuberculosis drug-resistant isolates from HIV- and HIV+ tuberculosis patients in Russia.

机构信息

National Medical Research Center of Phthisiopulmonology and Infectious Diseases, Ministry of Public Heath of the Russian Federation (NMRC PhID), Moscow, Russian Federation.

Ural Research Institute of Phthisiopulmonology -Branch of NMRC PhID, Ekaterinburg, Russian Federation.

出版信息

BMC Microbiol. 2022 May 19;22(1):138. doi: 10.1186/s12866-022-02553-7.

DOI:10.1186/s12866-022-02553-7
PMID:35590243
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9118847/
Abstract

BACKGROUND

High burden of drug-resistant (DR) tuberculosis (TB) is a significant threat to national TB control programs all over the world and in the Russian Federation. Different Mycobacterium tuberculosis (MTB) genotypes are hypothesized to have specific characteristics affecting TB control programs. For example, Beijing strains are supposed to have higher mutation rates compared to strains of other genotypes and subsequently higher capability to develop drug-resistance.

RESULTS

Clinical MTB isolates from HIV- and HIV+ patients from four regions of Russia were analyzed for genotypes and mutations conferring resistance to Isoniazid, Rifampicin, Ethambutol, aminoglycosides, and fluoroquinolones. Analysis of genotypes and polymorphism of genomic loci according to the HIV status of the patients - sources of MTB isolates were performed. Studied MTB isolates from HIV- TB patients belonged to 15 genotypes and from HIV + TB patients - to 6 genotypes. Beijing clinical isolates dominated in HIV- (64,7%) and HIV+ (74,4%) groups. Other isolates were of LAM (including LAM1 and LAM9), Ural, and 4 minor groups of genotypes (including 5 subclones T). The spectrum of genotypes in the HIV- group was broader than in the HIV+ group. PR of B0/W148 Beijing was significantly lower than of other Beijing genotypes in susceptible and MDR-XDR isolates. Rates of isolates belonging to non-Beijing genotypes were higher than Beijing in susceptible isolates from HIV- patients.

CONCLUSIONS

Beijing genotype isolates prevailed in clinical isolates of all drug susceptibility profiles both from HIV- and HIV+ patients, although B0/W148 Beijing genotype did not dominate in this study. Genome loci and mutations polymorphisms were more pronounced in clinical isolates from HIV- patients, than from HIV+.

摘要

背景

耐药结核病(TB)负担高是全球和俄罗斯国家结核病控制规划的重大威胁。不同的结核分枝杆菌(MTB)基因型被假设具有影响结核病控制规划的特定特征。例如,与其他基因型的菌株相比,北京菌株的突变率更高,因此更有可能产生耐药性。

结果

对来自俄罗斯四个地区的 HIV-和 HIV+患者的临床 MTB 分离株进行了基因型和导致异烟肼、利福平、乙胺丁醇、氨基糖苷类和氟喹诺酮类耐药的突变分析。根据 MTB 分离株来源的 HIV 状态分析了基因型和基因组位点的多态性。研究的 HIV-结核病患者的 MTB 分离株属于 15 种基因型,HIV+结核病患者的 MTB 分离株属于 6 种基因型。北京临床分离株在 HIV-(64.7%)和 HIV+(74.4%)组中占主导地位。其他分离株为 LAM(包括 LAM1 和 LAM9)、乌拉尔和 4 种较小的基因型组(包括 5 个子克隆 T)。HIV-组的基因型谱比 HIV+组更广泛。在敏感和 MDR-XDR 分离株中,B0/W148 北京的 PR 明显低于其他北京基因型。在 HIV-患者的敏感分离株中,属于非北京基因型的分离株的比例高于北京。

结论

北京基因型分离株在 HIV-和 HIV+患者的所有药物敏感性谱的临床分离株中均占优势,尽管 B0/W148 北京基因型在本研究中并未占主导地位。与 HIV+相比,HIV-患者的临床分离株中基因组位点和突变多态性更为明显。

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