Cell cycle control and environmental response by second messengers in Caulobacter crescentus
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RESEARCH
Open Access
Cell cycle control and environmental response by second messengers in Caulobacter crescentus Chunrui Xu1† , Bronson R. Weston1† , John J. Tyson2 and Yang Cao3* From The Sixth International Workshop on Computational Network Biology: Modeling, Analysis, and Control (CNB-MAC 2019) Niagara Falls, NY, USA. 07 September 2019 *Correspondence: [email protected] † Chunrui Xu and Bronson Weston contributed equally to this work. 3 Department of Computer Science, Virginia Tech, 24061 Blacksburg, VA, USA Full list of author information is available at the end of the article
Abstract Background: Second messengers, c-di-GMP and (p)ppGpp, are vital regulatory molecules in bacteria, influencing cellular processes such as biofilm formation, transcription, virulence, quorum sensing, and proliferation. While c-di-GMP and (p)ppGpp are both synthesized from GTP molecules, they play antagonistic roles in regulating the cell cycle. In C. crescentus, c-di-GMP works as a major regulator of pole morphogenesis and cell development. It inhibits cell motility and promotes S-phase entry by inhibiting the activity of the master regulator, CtrA. Intracellular (p)ppGpp accumulates under starvation, which helps bacteria to survive under stressful conditions through regulating nucleotide levels and halting proliferation. (p)ppGpp responds to nitrogen levels through RelA-SpoT homolog enzymes, detecting glutamine concentration using a nitrogen phosphotransferase system (PTSNtr ). This work relates the guanine nucleotide-based second messenger regulatory network with the bacterial PTSNtr system and investigates how bacteria respond to nutrient availability. Results: We propose a mathematical model for the dynamics of c-di-GMP and (p)ppGpp in C. crescentus and analyze how the guanine nucleotide-based second messenger system responds to certain environmental changes communicated through the PTSNtr system. Our mathematical model consists of seven ODEs describing the dynamics of nucleotides and PTSNtr enzymes. Our simulations are consistent with experimental observations and suggest, among other predictions, that SpoT can effectively decrease c-di-GMP levels in response to nitrogen starvation just as well as it increases (p)ppGpp levels. Thus, the activity of SpoT (or its homologues in other bacterial species) can likely influence the cell cycle by influencing both c-di-GMP and (p)ppGpp. (Continued on next page)
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