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首次深入了解来自感染 HIV 的墨西哥患者的结核分枝杆菌分离株的遗传多样性和导致耐多药的突变。

First insights into the genetic diversity of Mycobacterium tuberculosis isolates from HIV-infected Mexican patients and mutations causing multidrug resistance.

机构信息

Departamento de Microbiologia, ENCB-IPN, Mexico City, Mexico.

出版信息

BMC Microbiol. 2010 Mar 17;10:82. doi: 10.1186/1471-2180-10-82.

Abstract

BACKGROUND

The prevalence of infections with Mycobacterium tuberculosis (MTb) and nontuberculous mycobacteria (NTM) species in HIV-infected patients in Mexico is unknown. The aims of this study were to determine the frequency of MTb and NTM species in HIV-infected patients from Mexico City, to evaluate the genotypic diversity of the Mycobacterium tuberculosis complex strains, to determine their drug resistance profiles by colorimetric microplate Alamar Blue assay (MABA), and finally, to detect mutations present in katG, rpoB and inhA genes, resulting in isoniazid (INH) and rifampin (RIF) resistance.

RESULTS

Of the 67 mycobacterial strains isolated, 48 were identified as MTb, 9 as M. bovis, 9 as M. avium and 1 as M. intracellulare. IS6110-RFLP of 48 MTb strains showed 27 profiles. Spoligotyping of the 48 MTb strains yielded 21 patterns, and 9 M. bovis strains produced 7 patterns. Eleven new spoligotypes patterns were found. A total of 40 patterns were produced from the 48 MTb strains when MIRU-VNTR was performed. Nineteen (39.6%) MTb strains were resistant to one or more drugs. One (2.1%) multidrug-resistant (MDR) strain was identified. A novel mutation was identified in a RIF-resistant strain, GAG --> TCG (Glu --> Ser) at codon 469 of rpoB gene.

CONCLUSIONS

This is the first molecular analysis of mycobacteria isolated from HIV-infected patients in Mexico, which describe the prevalence of different mycobacterial species in this population. A high genetic diversity of MTb strains was identified. New spoligotypes and MIRU-VNTR patterns as well as a novel mutation associated to RIF-resistance were found. This information will facilitate the tracking of different mycobacterial species in HIV-infected individuals, and monitoring the spread of these microorganisms, leading to more appropriate measures for tuberculosis control.

摘要

背景

在墨西哥感染结核分枝杆菌(MTb)和非结核分枝杆菌(NTM)的 HIV 感染者的流行情况尚不清楚。本研究的目的是确定来自墨西哥城的 HIV 感染者中 MTb 和 NTM 物种的频率,评估结核分枝杆菌复合菌株的基因型多样性,通过比色微板 Alamar Blue 测定法(MABA)确定其耐药谱,最后,检测 katG、rpoB 和 inhA 基因中导致异烟肼(INH)和利福平(RIF)耐药的突变。

结果

在分离的 67 株分枝杆菌中,48 株鉴定为 MTb,9 株为牛分枝杆菌,9 株为鸟分枝杆菌,1 株为胞内分枝杆菌。48 株 MTb 菌株的 IS6110-RFLP 显示 27 种谱型。48 株 MTb 菌株 spoligotyping 产生 21 种模式,9 株牛分枝杆菌产生 7 种模式。发现了 11 种新 spoligotype 模式。对 48 株 MTb 菌株进行 MIRU-VNTR 时共产生 40 种模式。40 株 MTb 菌株中有 19 株(39.6%)对一种或多种药物耐药。鉴定出 1 株(2.1%)耐多药(MDR)菌株。在 1 株 RIF 耐药株中发现了一种新的突变,rpoB 基因 469 密码子处的 GAG 到 TCG(Glu 到 Ser)。

结论

这是墨西哥首例对 HIV 感染者分离的分枝杆菌进行的分子分析,描述了该人群中不同分枝杆菌物种的流行情况。鉴定出 MTb 菌株的遗传多样性较高。发现了新的 spoligotype 和 MIRU-VNTR 模式以及与 RIF 耐药相关的新突变。这些信息将有助于跟踪 HIV 感染者中不同的分枝杆菌物种,并监测这些微生物的传播,从而采取更合适的结核病控制措施。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c56b/2848023/9e4084e635f2/1471-2180-10-82-1.jpg

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