Cyclic di-GMP sensing histidine kinase PdtaS controls mycobacterial adaptation to carbon sources

Hariharan, VN and Yadav, R and Thakur, C and Singh, A and Gopinathan, R and Singh, DP and Sankhe, G and Malhotra, V and Chandra, N and Bhatt, A and Saini, DK (2021) Cyclic di-GMP sensing histidine kinase PdtaS controls mycobacterial adaptation to carbon sources. In: FASEB Journal, 35 (4).

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Abstract

Cell signaling relies on second messengers to transduce signals from the sensory apparatus to downstream signaling pathway components. In bacteria, one of the most important and ubiquitous second messenger is the small molecule cyclic diguanosine monophosphate (c-di-GMP). While the biosynthesis, degradation, and regulatory pathways controlled by c-di-GMP are well characterized, the mechanisms through which c-di-GMP controls these processes are not entirely understood. Herein we present the report of a c-di-GMP sensing sensor histidine kinase PdtaS (Rv3220c), which binds to c-di-GMP at submicromolar concentrations, subsequently perturbing signaling of the PdtaS-PdtaR (Rv1626) two-component system. Aided by biochemical analysis, genetics, molecular docking, FRET microscopy, and structural modelling, we have characterized the binding of c-di-GMP in the GAF domain of PdtaS. We show that a pdtaS knockout in Mycobacterium smegmatis is severely compromised in growth on amino acid deficient media and exhibits global transcriptional dysregulation. The perturbation of the c-di-GMP-PdtaS-PdtaR axis results in a cascade of cellular changes recorded by a multiparametric systems� approach of transcriptomics, unbiased metabolomics, and lipid analyses. © 2021 Federation of American Societies for Experimental Biology

Item Type:	Journal Article
Publication:	FASEB Journal
Publisher:	John Wiley and Sons Inc
Additional Information:	The copyright for this article belongs to John Wiley and Sons Inc
Department/Centre:	Division of Biological Sciences > Biochemistry Division of Biological Sciences > Molecular Reproduction, Development & Genetics Division of Interdisciplinary Sciences > Centre for Biosystems Science and Engineering
Date Deposited:	13 Jul 2021 09:22
Last Modified:	13 Jul 2021 09:22
URI:	http://eprints.iisc.ac.in/id/eprint/68714

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