Mycobacterium tuberculosis PknK Substrate Profiling Reveals Essential Transcription Terminator Protein Rho and Two-Component Response Regulators PrrA and MtrA as Novel Targets for Phosphorylation.
Mycobacterium tuberculosis PknK Substrate Profiling Reveals Essential Transcription Terminator Protein Rho and Two-Component Response Regulators PrrA and MtrA as Novel Targets for Phosphorylation.
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结核分枝杆菌PknK底物分析揭示了必需的转录终止子蛋白Rho和双组分反应调节因子PrrA和MtrA作为磷酸化的新靶点
DOI：
10.1128/spectrum.01354-21
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发表时间：
2022-04-27
影响因子：
3.7
通讯作者：
Saini, Deepak Kumar
中科院分区：
文献类型：
--
作者：
Malhotra, Vandana;Okon, Blessing P.;Satsangi, Akash T.;Das, Sumana;Waturuocha, Uchenna Watson;Vashist, Atul;Clark-Curtiss, Josephine E.;Saini, Deepak Kumar
关键词：
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 ΔpknK 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. IMPORTANCE Networks of gene regulation and signaling cascades are fundamental to the pathogenesis of Mycobacterium tuberculosis in adapting to the continuously changing intracellular environment in the host. M. tuberculosis protein kinase K is a transcription regulator that responds to diverse environmental signals and facilitates stress-induced growth adaptation in culture and during infection. This study identifies multiple signaling interactions of PknK and provides evidence that PknK can change the transcriptional landscape during growth transitions by connecting distinctly different signal transduction and regulatory pathways essential for mycobacterial survival.
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DOI：
10.1007/s12275-015-5333-8
发表时间：
2015-11
期刊：
Journal of microbiology (Seoul, Korea)
影响因子：
--
作者：
Korch SB;Malhotra V;Contreras H;Clark-Curtiss JE
通讯作者：
Clark-Curtiss JE
影响因子：
4.8
作者：
Bhatt K;Machado H;Osório NS;Sousa J;Cardoso F;Magalhães C;Chen B;Chen M;Kim J;Singh A;Ferreira CM;Castro AG;Torrado E;Jacobs WR Jr;Bhatt A;Saraiva M
通讯作者：
Saraiva M
DOI：
10.1016/j.bbapap.2009.09.008
发表时间：
2010-03-01
影响因子：
3.2
作者：
Chao, Joseph;Wong, Dennis;Av-Gay, Yossef
通讯作者：
Av-Gay, Yossef
影响因子：
4.8
作者：
Baer, Christina E.;Iavarone, Anthony T.;Sassetti, Christopher M.
通讯作者：
Sassetti, Christopher M.
影响因子：
10.5
作者：
Kang, CM;Abbott, DW;Husson, RN
通讯作者：
Husson, RN