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

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.

Keywords: Antibiotic resistance; Epigenetics; MicroRNA; Tuberculosis.