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Cyclic di‐GMP sensing histidine kinase PdtaS controls mycobacterial adaptation to carbon sources
Author(s) -
Hariharan Vignesh Narayan,
Yadav Rahul,
Thakur Chandrani,
Singh Albel,
Gopinathan Renu,
Singh Devendra Pratap,
Sankhe Gaurav,
Malhotra Vandana,
Chandra Nagasuma,
Bhatt Apoorva,
Saini Deepak Kumar
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.202002537rr
Subject(s) - histidine kinase , adaptation (eye) , kinase , chemistry , histidine , biology , biochemistry , enzyme , neuroscience
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.