Investigating a putative transcriptional regulatory protein encoded by Rv1719 gene of Mycobacterium tuberculosis

Pandey, Manitosh; Tiwari, Satish; Johri, Sonia; Biswal, B.K.; Sharma, Chandresh; Pandey, Amit

doi:10.1007/s10930-022-10062-9

Cited by 1 publication

(1 citation statement)

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“…Adaptation to harsh and changing environments by organisms is attributed to precise gene regulation controlled by a multitude of proteins 19 . These include nucleoid associated proteins (NAPs): a group of small but abundant DNA binding proteins that organize DNA into compact structures and influence transcription 20 – 23 .…”

Section: Introductionmentioning

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

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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.

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Section: Introductionmentioning

confidence: 99%