Epigenetic code during mycobacterial infections: therapeutic implications for tuberculosis

Abstract

Epigenetics involves changing the gene function without any change in the sequence of the genes. In the case of tuberculosis (TB) infections, the bacilli, Mycobacterium tuberculosis (M.tb) uses epigenetics as a tool to protect itself from the host immune system. TB is a deadly disease-causing maximum death per year due to a single infectious agent. In the case of TB, there is an urgent need for novel host-directed therapies which can effectively target the survival and long term persistence of the bacteria without developing drug resistance in the bacterial strains while also reducing the duration and toxicity associated with the mainstream anti-TB drugs. Recent studies have suggested that TB infection has a significant effect on the host epigenome thereby manipulating the host immune response in the favor of the pathogen. M.tb alters the activation status of key genes involved in the immune response against TB to promote its survival and subvert the antibacterial strategies of the host. These changes are reversible and can be exploited to design very efficient host-directed therapies to fight against TB. This review has been written with the purpose of discussing the role of epigenetic changes in TB pathogenesis and the therapeutic approaches involving epigenetics, which can be utilized for targeting the pathogen.

Infection and immunity: ‘There Are Things Out There You (Don't) Need To Know About’

“…Fatima et al. [19] provide a broad overview of the different epigenetic modifications and discuss their reversibility in order to improve current host‐directed therapies against tuberculosis.…”

“…Mtb is also using epigenetic modifications to evade host immunity, and recent studies have shown that in turn, Mtb infections affect the host epigenome to favour pathogenic survival. Fatima et al [19] provide a broad overview of the different epigenetic modifications and discuss their reversibility in order to improve current host-directed therapies against tuberculosis.…”

Modulation of the Response to Mycobacterium leprae and Pathogenesis of Leprosy

“…Epigenetic markers that confer specific phenotypes have a great potential as biomarkers for the diagnosis and progression of diseases ( Figure 2 ; Batista et al, 2020 ; Fatima et al, 2021 ). Moreover, epigenetic regulation is also a quick response to changes in the environment and may be reversible.…”

“…miRNAs are involved in the epigenetic mechanisms of regulation of cell development, proliferation, differentiation, apoptosis and even anti-inflammatory and pro-inflammatory stimuli. MiRNAs promote a dual role in M. tuberculosis infection, persistence, and host immune system modulation ( Batista et al, 2020 ; Fatima et al, 2021 ). These molecules have great potential as biomarkers for diagnosis of disease and its progression to disease.…”

mbtD and celA1 association with ethambutol resistance in Mycobacterium tuberculosis: A multiomics analysis

“…Over the past decade, epigenetic mechanisms have become increasingly important in our understanding of pathogenicity, host immunity, hypoxic survival, and virulence. Epigenetics can affect gene expression without altering the DNA sequence, not only in eukaryotes but also in bacteria, in which DNA methylation is one of the main epigenetic mechanisms for the regulation of gene expression ( Fatima et al., 2021 ). Studies on the correlation between DNA methylation and mechanisms of drug resistance in Mtb have recently attracted extensive attention.…”