Lokesh Kumar

Washington University in St. Louis

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Sunish Kumar Radhakrishnan

Indian Institute of Science Education and Research Pune

Sharath Narayanan

Manipal University Jaipur

Chevaughn Waller

Columbia University Irving Medical Center

Coralie Fumeaux

Harvard University

Manisha Siwach

Indian Institute of Science Education and Research Pune

Soumyajit Sanyal

King George's Medical University

Gaël Panis

University of Geneva

Saravanan Palani

Indian Institute of Science Bangalore

Balaganesh Janakiraman

Tata Institute of Fundamental Research

Ekaterina Batourina

Columbia University Irving Medical Center

Cooperative Institutions

Indian Institute of Science Education and Research Thiruvananthapuram

University of Geneva

Columbia University Irving Medical Center

Case Western Reserve University

University of Lausanne

Indian Institute of Science Education and Research Pune

University of Warwick

Tata Institute of Fundamental Research

Columbia University

Washington University in St. Louis

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Nur77 protects the bladder urothelium from intracellular bacterial infection

Nature Communications (2024)

Christina A. Collins Chevaughn Waller Ekaterina Batourina Lokesh Kumar Cathy Mendelsohn

Intracellular parasite

10.1038/s41467-024-52454-8

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A cell cycle-controlled redox switch regulates the topoisomerase IV activity

Genes & Development (2015)

Sharath Narayanan Balaganesh Janakiraman Lokesh Kumar Sunish Kumar Radhakrishnan

Topoisomerase IV (topo IV), an essential factor during chromosome segregation, resolves the catenated chromosomes at the end of each replication cycle. How the decatenating activity of the topo IV is regulated during the early stages of the chromosome cycle despite being in continuous association with the chromosome remains poorly understood. Here we report a novel cell cycle-regulated protein in Caulobacter crescentus , NstA (negative switch for topo IV decatenation activity), that inhibits the decatenation activity of the topo IV during early stages of the cell cycle. We demonstrate that in C. crescentus , NstA acts by binding to the ParC DNA-binding subunit of topo IV. Most importantly, we uncover a dynamic oscillation of the intracellular redox state during the cell cycle, which correlates with and controls NstA activity. Thus, we propose that predetermined dynamic intracellular redox fluctuations may act as a global regulatory switch to control cellular development and cell cycle progression and may help retain pathogens in a suitable cell cycle state when encountering redox stress from the host immune response.

Caulobacter crescentus

10.1101/gad.257030.114

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Sensory domain of the cell cycle kinase CckA regulates the differential DNA binding of the master regulator CtrA in Caulobacter crescentus

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms (2018)

Sharath Narayanan Lokesh Kumar Sunish Kumar Radhakrishnan

Sophisticated signaling mechanisms allow bacterial cells to cope with environmental and intracellular challenges. Activation of specific pathways ameliorates these challenges and thereby warrants integrity. Here, we demonstrate the pliability of the CckA-CtrA two-component signaling system in the freshwater bacterium Caulobacter crescentus. Our forward genetic screen to analyze suppressor mutations that can negate the chromosome segregation block induced by the topoisomerase IV inhibitor, NstA, yielded various point mutations in the cell cycle histidine kinase, CckA. Notably, we identified a point mutation in the PAS-B domain of CckA, which resulted in increased levels of phosphorylated CtrA (CtrA~P), the master cell cycle regulator. Surprisingly, this increase in CtrA~P levels did not translate into a genome-wide increase in the DNA occupancy of CtrA, but specifically enriched its affinity for the chromosomal origin of replication, C

Caulobacter crescentus

Histidine kinase

Response regulator

10.1016/j.bbagrm.2018.08.006

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Sensory domain of the cell cycle kinase CckA inCaulobacter crescentusregulates the differential DNA binding activity of the master regulator CtrA

bioRxiv (Cold Spring Harbor Laboratory) (2018)

Sharath Narayanan Lokesh Kumar Sunish Kumar Radhakrishnan

Sophisticated signaling mechanisms allow bacterial cells to cope with environmental and intracellular challenges. Activation of specific pathways facilitates the cells to overcome cellular damage and thereby warrant integrity. Here we demonstrate the pliability of the CckA-CtrA two component signaling system in the freshwater bacterium Caulobacter crescentus . Our forward genetic screen to analyse suppressor mutations that can negate the chromosome segregation block induced by the topoisomerase IV inhibitor, NstA, yielded various point mutations in the cell cycle histidine kinase, CckA. Notably, we identified a point mutation in the PAS-B domain of CckA, which resulted in increased levels of phosphorylated CtrA (CtrA~P), the master cell cycle regulator. Surprisingly, this increase in CtrA~P levels did not translate into a genome-wide increase in the DNA occupancy of CtrA, but specifically enriched its affinity to the chromosomal origin of replication, C ori , and a very small sub-set of CtrA regulated promoters. We show that through this enhanced binding of CtrA to the C ori , cells are able to overcome the toxic defects rendered by stable NstA through a possible slow down in the chromosome cycle. Taken together, our work opens up an unexplored and intriguing aspect of the CckA-CtrA signal transduction pathway. The distinctive DNA binding nature of CtrA and its regulation by CckA might also be crucial for pathogenesis because of the highly conserved nature of CckA-CtrA pathway in alphaproteobacteria.

Caulobacter crescentus

Histidine kinase

Response regulator

10.1101/300178

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An organelle-tethering mechanism couples flagellation to cell division in bacteria

Developmental Cell (2021)

Manisha Siwach Lokesh Kumar Saravanan Palani Samada Muraleedharan Gaël Panis

Caulobacter crescentus

rpoN

10.1016/j.devcel.2021.01.013

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Citations (12)