Epigenetic changes in Mycobacterium tuberculosis and its host provide potential targets or biomarkers for drug discovery and clinical diagnosis

Sui, Jing; Qiao, Wenliang; Xiang, Xinrong; Luo, Youfu

doi:10.1016/j.phrs.2022.106195

Cited by 14 publications

(5 citation statements)

References 166 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…6 C). It has been shown that in response to environmental cues, post-translational modification (acetylation and phosphorylation) of NAPs including MDP1 affects DNA binding, thus influencing nucleoid architecture and ultimately gene expression 21 , 24 , 30 , 54 , 55 . Taken together, our results indicate that as a NAP, MDP1 in BCG is a general gene repressor, and suggests that MDP1 is able to alter bacterial gene expression to aid in BCG adaptation to stress.…”

Section: Discussionmentioning

confidence: 99%

Mycobacterial DNA-binding protein 1 is critical for BCG survival in stressful environments and simultaneously regulates gene expression

Shaban,

Gebretsadik,

Hakamata

et al. 2023

Sci Rep

View full text Add to dashboard Cite

Survival of the live attenuated Bacillus Calmette-Guérin (BCG) vaccine amidst harsh host environments is key for BCG effectiveness as it allows continuous immune response induction and protection against tuberculosis. Mycobacterial DNA binding protein 1 (MDP1), a nucleoid associated protein, is essential in BCG. However, there is limited knowledge on the extent of MDP1 gene regulation and how this influences BCG survival. Here, we demonstrate that MDP1 conditional knockdown (cKD) BCG grows slower than vector control in vitro, and dies faster upon exposure to antibiotics (bedaquiline) and oxidative stress (H2O2 and menadione). MDP1-cKD BCG also exhibited low infectivity and survival in THP-1 macrophages and mice indicating possible susceptibility to host mediated stress. Consequently, low in vivo survival resulted in reduced cytokine (IFN-gamma and TNF-alpha) production by splenocytes. Temporal transcriptome profiling showed more upregulated (81–240) than downregulated (5–175) genes in response to MDP1 suppression. Pathway analysis showed suppression of biosynthetic pathways that coincide with low in vitro growth. Notable was the deferential expression of genes involved in stress response (sigI), maintenance of DNA integrity (mutT1), REDOX balance (WhiB3), and host interactions (PE/PE_PGRS). Thus, this study shows MDP1’s importance in BCG survival and highlights MDP1-dependent gene regulation suggesting its role in growth and stress adaptation.

show abstract

Section: Discussionmentioning

confidence: 99%

Mycobacterial DNA-binding protein 1 is critical for BCG survival in stressful environments and simultaneously regulates gene expression

Shaban,

Gebretsadik,

Hakamata

et al. 2023

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Such epigenetic mechanisms are known to be involved in the G. mellonella response to infection with L. monocytogenes : detailed in the ‘Immune response of G. mellonella to L. monocytogenes ’ section above, as they are in the human response to infection to that pathogen (reviewed in Bierne and Hamon 2020 ). Epigenetic mammalian host responses have also been described after infection of cell lines and/or animals with many intracellular bacterial pathogens (reviewed in Fol et al 2020 ), including, relevant to this review, B. pseudomallei (Cizmeci D et al 2016 ), and M. tuberculosis (reviewed in Fatima et al 2022 ), where there is extensive interest because of the potential for developing new and diagnostic biomarkers and therapeutics (Sui et al 2022 ). A recent study indicated that miRNAs have a role in the epigenetic reprogramming of innate immunity in G. mellonella larvae such that pathogenic and commensal E. coli could be distinguished (Mukherjee et al 2020 ).…”

Section: Future Prospectsmentioning

confidence: 99%

Galleria mellonella–intracellular bacteria pathogen infection models: the ins and outs

Asai

Newton

et al. 2023

FEMS Microbiology Reviews

View full text Add to dashboard Cite

Galleria mellonella (greater wax moth) larvae are used widely as surrogate infectious disease models, due to ease of use and the presence of an innate immune system functionally similar to that of vertebrates. Here we review G. mellonella-human intracellular bacteria pathogen infection models from the genera Burkholderia, Coxiella, Francisella, Listeria, and Mycobacterium. For all genera, G. mellonella use has increased understanding of host-bacterial interactive biology, particularly through studies comparing the virulence of closely related species and/or wild-type versus mutant pairs. In many cases, virulence in G. mellonella mirrors that found in mammalian infection models, although it is unclear whether the pathogenic mechanisms are the same. The use of G. mellonella larvae has speeded up in vivo efficacy and toxicity testing of novel antimicrobials to treat infections caused by intracellular bacteria: an area that will expand since the FDA no longer requires animal testing for licensure. Further use of G. mellonella-intracellular bacteria infection models will be driven by advances in G. mellonella genetics, imaging, metabolomics, proteomics, and transcriptomic methodologies, alongside the development and accessibility of reagents to quantify immune markers, all of which will be underpinned by a fully annotated genome.

show abstract

“…By employing an efflux pump regulatory network (EPRN) model in E. coli strains, Motta et al demonstrated that the epigenetic inheritance of transcription rates in genes related to EPRN is essential for acquiring adaptive resistance within a bacterial population [ 52 ]. DNA methylation within promoters of virulence genes in Mycobacterium tuberculosis and Campylobacter jejuni has been identified, offering potential targets or biomarkers for drug discovery and clinical diagnosis [ 53 , 54 ]. Additionally, DNA cytosine methylation can be employed to control physiological processes and antibiotics production in several bacterial strains.…”

Section: Introductionmentioning

confidence: 99%

Emerging methylation-based approaches in microbiome engineering

Won,

Yim

2024

Biotechnol Biofuels

View full text Add to dashboard Cite

Bacterial epigenetics, particularly through DNA methylation, exerts significant influence over various biological processes such as DNA replication, uptake, and gene regulation in bacteria. In this review, we explore recent advances in characterizing bacterial epigenomes, accompanied by emerging strategies that harness bacterial epigenetics to elucidate and engineer diverse bacterial species with precision and effectiveness. Furthermore, we delve into the potential of epigenetic modifications to steer microbial functions and influence community dynamics, offering promising opportunities for understanding and modulating microbiomes. Additionally, we investigate the extensive diversity of DNA methyltransferases and emphasize their potential utility in the context of the human microbiome. In summary, this review highlights the potential of DNA methylation as a powerful toolkit for engineering microbiomes.

show abstract

Epigenetic changes in Mycobacterium tuberculosis and its host provide potential targets or biomarkers for drug discovery and clinical diagnosis

Cited by 14 publications

References 166 publications

Mycobacterial DNA-binding protein 1 is critical for BCG survival in stressful environments and simultaneously regulates gene expression

Mycobacterial DNA-binding protein 1 is critical for BCG survival in stressful environments and simultaneously regulates gene expression

Galleria mellonella–intracellular bacteria pathogen infection models: the ins and outs

Emerging methylation-based approaches in microbiome engineering

Contact Info

Product

Resources

About