Abstract
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, Cori, and for a very small sub-set of CtrA regulated promoters. We show that through this enhanced binding of CtrA to the Cori, cells are able to overcome the toxic defects rendered by stable NstA through a possible slow down in the chromosome replication 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 the CckA-CtrA pathway in alphaproteobacteria.
Highlights
Bacteria harbor robust signaling mechanisms to tolerate stressful conditions
The L228P mutation, which mapped to the PAS-B domain in CckA, rendered developmental defects such as cell filamentation in the wild-type (WT) and the ∆nstA mutant (Fig. 1D, Supplementary Fig. S2A)
While in Caulobacter CtrA is involved in cellfate control, and cell cycle, by fine-tuning the stalked and swarmer cell programs, the control of cell envelope composition by CtrA is crucial in B. abortus and Rhizobium leguminosarum [53,54], thereby reiterating the plasticity of CckA-CtrA pathway
Summary
Bacteria harbor robust signaling mechanisms to tolerate stressful conditions. The aquatic α‐proteobacterium, Caulobacter crescentus ( Caulobacter), has emerged as a powerful model organism for studying the complex signaling mechanisms that control cell cycle and development in response to environmental cues. One of the daughter cells, the swarmer cell, is motile and its locomotion is assisted by the polar flagellum [1,2]. The G1-like swarmer cell has to terminally differentiate into a stalked cell to enter into the proliferative phase. This G1 to S-like transition is marked by the shedding of the flagellum, retraction of the pili, and production of a stalk at the same cell pole
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