Malhotra, V and Okon, BP and Satsangi, AT and Das, S and Waturuocha, UW and Vashist, A and Clark-Curtiss, JE and Saini, DK (2022) Mycobacterium tuberculosis PknK Substrate Profiling Reveals Essential Transcription Terminator Protein Rho and Two- Component Response Regulators PrrA and MtrA as Novel Targets for Phosphorylation. In: Microbiology Spectrum, 10 (2).
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Abstract
The Mycobacterium tuberculosis protein kinase K regulates growth adaptation by facilitating mycobacterial survival in response to a variety of in vitro and in vivo stress conditions. Here, we further add that pknK transcription is responsive to carbon and nitrogen starvation signals. The increased survival of an M. tuberculosis DpknK mutant strain under carbon- and nitrogen-limiting growth conditions compared to the wild-type (WT) H37Rv suggests an integral role of PknK in regulating growth during metabolic stress. To identify the downstream targets of PknK-mediated signaling, we compared phosphoproteomic and transcription profiles of mycobacterial strains overexpressing WT and phosphorylation-defective PknK. Results implicate PknK as a signaling protein that can regulate several enzymes involved in central metabolism, transcription regulation, and signal transduction. A key finding of this study was the identification of two essential two-component response regulator (RR) proteins, PrrA and MtrA, and Rho transcription terminator, as unique targets for PknK. We confirm that PknK interacts with and phosphorylates PrrA, MtrA, and Rho in vivo. PknK-mediated phosphorylation of MtrA appears to increase binding of the RR to the cognate probe DNA. However, dual phosphorylation of MtrA and PrrA response regulators by PknK and their respective cognate sensor kinases in vitro showed nominal additive effect on the mobility of the protein-DNA complex, suggesting the presence of a potential fine-tuning of the signal transduction pathway which might respond to multiple cues. © 2022 Malhotra et al.
| Item Type: | Journal Article |
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| Publication: | Microbiology Spectrum |
| Publisher: | American Society for Microbiology |
| Additional Information: | The copyright for this article belongs to the authors. |
| Keywords: | bacterial protein; carbon; DNA; nitrogen; protein kinase, gene expression regulation; genetics; human; metabolism; Mycobacterium tuberculosis; phosphorylation; tuberculosis, Bacterial Proteins; Carbon; DNA; Gene Expression Regulation, Bacterial; Humans; Mycobacterium tuberculosis; Nitrogen; Phosphorylation; Protein Kinases; Tuberculosis |
| Department/Centre: | Division of Biological Sciences > Molecular Reproduction, Development & Genetics |
| Date Deposited: | 29 Sep 2022 11:52 |
| Last Modified: | 29 Sep 2022 11:52 |
| URI: | https://eprints.iisc.ac.in/id/eprint/76834 |
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