A review of the human microRNA and the Mycobacterium tuberculosis epigenetic effects on the emergence drug resistance

IF 5.2 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences Pub Date : 2025-04-24 DOI:10.1016/j.lfs.2025.123637

Yashna Sukdeo, Nozibusiso Pearl Shozi, Nonsikelelo Ndimande, Kingsley Chimaeze Mbara, Peter M.O. Owira

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引用次数: 0

Abstract

Aims

Mycobacterium tuberculosis (MTB) uses epigenetics to avoid the hostile host immune defence systems and also mount resistance to chemotherapy when exposed to antibiotic stress. MTB's epigenetic survival tool-kit includes genomic DNA histone acetylation/deacetylation, methylation, phosphorylation, ubiquitylation, etc. The non-coding host microRNAs (miRNAs) as genomic products of epigenetic control of drug extrusion processes, drug permeability barrier formation or metabolism, and target alteration are hijacked by MTB to mount multi-drug resistance. The miRNAs involved and the mechanisms used are not yet completely understood. The role of MTB genome-derived miRNA are currently indeterminate as the current studies are only focused on the host miRNA biogenesis in MTB pathogenesis. However, the contribution of host miRNA to drug resistance in MTB chemotherapy is largely unknown.

Materials and methods

We have comprehensively searched online databases for medical, health, and nanotechnology for articles published in English between 2020 and 2024 using search words “MTB”, “Epigenetics”, “microRNA”, “TB Chemotherapy” to compile this narrative review.

Key findings

MTB epigenetic tool-kit of DNA methylation, histone acetylation/deacetylation, cell membrane impermeability, drug metabolism and target mimicry are mediated by the hijacked host cell microRNAs in the development of drug resistance. Antisense oligomers or mimetics can therefore, be used as miRNA antagonists/silencers or agomirs, respectively, depending on the pattern of miRNA expression, to combat resistance to MTB chemotherapy.

Conclusions

This review discusses microRNAs as epigenetic agents in the emergence of Multi-Drug Resistance TB (MDR-TB) and their potential role in chemotherapeutics.

Abstract Image

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人microRNA与结核分枝杆菌出现耐药的表观遗传效应研究进展

目的：结核分枝杆菌（MTB）利用表观遗传学来避开敌对宿主的免疫防御系统，并在暴露于抗生素压力时对化疗产生耐药性。MTB的表观遗传生存工具包包括基因组DNA组蛋白乙酰化/去乙酰化、甲基化、磷酸化、泛素化等。非编码宿主microRNAs （miRNAs）作为表观遗传控制药物挤出过程、药物通透性屏障形成或代谢以及靶标改变的基因组产物，被MTB劫持以产生多药耐药。涉及的mirna和使用的机制尚未完全了解。由于目前的研究只关注宿主miRNA在MTB发病机制中的生物发生，因此MTB基因组源性miRNA的作用尚不明确。然而，宿主miRNA在MTB化疗耐药中的作用在很大程度上是未知的。材料和方法我们综合检索了医学、健康和纳米技术的在线数据库，检索了2020年至2024年间发表的英文文章，检索词为“MTB”、“表观遗传学”、“microRNA”、“TB Chemotherapy”，编制了这篇叙事综述。DNA甲基化、组蛋白乙酰化/去乙酰化、细胞膜不透性、药物代谢和靶标模仿是smtb表观遗传学工具箱中被劫持的宿主细胞microrna介导的耐药发展过程。因此，根据miRNA的表达模式，反义寡聚物或模拟物可以分别用作miRNA拮抗剂/沉默剂或agomir，以对抗MTB化疗的耐药性。结论本文综述了microRNAs作为表观遗传因子在耐多药结核病（MDR-TB）发生中的作用及其在化疗中的潜在作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Life sciences 医学-药学

CiteScore

12.20

自引率

1.60%

发文量

841

审稿时长

6 months

期刊介绍： Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed. The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.