Transcriptional Regulators in Bacillus anthracis: A Potent Biothreat Agent
Transcriptional regulators are highly dynamic modulator proteins that bind to the specific DNA targets. These achieve their regulatory effects via activators or promoters. Consequently, the gene transcription is either upregulated or downregulated. These
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Shikha Joon, Sonika Bhatnagar, and Rakesh Bhatnagar
Abstract
Transcriptional regulators are highly dynamic modulator proteins that bind to the specific DNA targets. These achieve their regulatory effects via activators or promoters. Consequently, the gene transcription is either upregulated or downregulated. These are known to be an integral component of the cell signaling and signal transduction cascade. CodY is a DNA-binding protein that regulates the transcription of several genes involved in crucial cellular activities. Bacillus anthracis is a potent biowarfare agent. Within the bacterium, the CodY targets include genes involved in metabolism, amino acid biosynthesis and transport, nitrogen assimilation, motility, biofilm formation, sporulation, and virulence. Owing to the vitality of the CodY protein in its anthrax pathogenesis, it becomes pertinent to broaden our horizon on its structural and functional attributes. Keywords
Bacillus anthracis · Anthrax · Transcriptional regulators · Sporulation · Virulence
S. Joon School of Biotechnology, Jawaharlal Nehru University, New Delhi, India S. Bhatnagar Computational and Structural Biology Lab, Department of Biological Sciences and Engineering, Netaji Subhas University of Technology, New Delhi, India R. Bhatnagar (*) Banaras Hindu University, Varanasi, Uttar Pradesh, India e-mail: [email protected] # Springer Nature Singapore Pte Ltd. 2021 R. Prasad et al. (eds.), Recent Developments in Microbial Technologies, Environmental and Microbial Biotechnology, https://doi.org/10.1007/978-981-15-4439-2_17
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Introduction
CodY is a prokaryotic transcriptional regulator present in Gram-positive bacteria with low G + C content in their genome. Its pleiotropism is well-demonstrated in the myriad cellular activities including, motility, competence, biofilm, and pellicle formation, and virulence in pathogenic bacteria (Ratnayake-Lecamwasam et al. 2001; Tu Quoc et al. 2007; Lemos et al. 2008; Majerczyk et al. 2010; Gopalani et al. 2016). CodY activity is governed by the intracellular concentration of GTP and Branched-chain amino acids (BCAAs). These effector molecules are known to stimulate the DNA-binding activity of CodY. Consequently, the genes under CodY regulation (e.g., sporulation and adaptation genes) are not transcribed. This usually occurs during the exponential phase of bacterial growth when the effectors are in abundance. On the contrary, the concentration of the effectors drops as the cell transits from the active to the stationary phase. This, in turn, abrogates the DNA-binding activity of CodY, and the genes under its regulation are rescued (Fig. 17.1) (Stenz et al. 2011). The binding site and the mechanism of interaction for the BCAAs and CodY are well-documented in various homologs (Villapakkam et al. 2009). However, little is known about the GTP and CodY (B. anthracis, in particular) interaction mechanism. Further, the residues involved and the biochemical processes that occur post-binding remain elusive. Reportedly, Co
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