Cyclic di‐GMP sensing histidine kinase PdtaS controls mycobacterial adaptation to carbon sources
| Autor: | Nagasuma Chandra, Gaurav D. Sankhe, Devendra Pratap Singh, Vandana Malhotra, Chandrani Thakur, Apoorva Bhatt, Deepak Kumar Saini, Albel Singh, Renu Gopinathan, Rahul Singh Yadav, Vignesh Narayan Hariharan |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cyclic di-GMP Cell signaling Histidine Kinase Mycobacterium smegmatis Second Messenger Systems Biochemistry Mycobacterium 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Bacterial Proteins Biosynthesis Genetics Molecular Biology Bacteria biology Histidine kinase Gene Expression Regulation Bacterial biology.organism_classification Small molecule Carbon Two-component regulatory system Cell biology Molecular Docking Simulation 030104 developmental biology chemistry Second messenger system 030217 neurology & neurosurgery Signal Transduction Biotechnology |
| Zdroj: | The FASEB Journal. 35 |
| ISSN: | 1530-6860 0892-6638 |
| DOI: | 10.1096/fj.202002537rr |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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