A Second Role for the Second Messenger Cyclic-di-GMP in E. coli: Arresting Cell Growth by Altering Metabolic Flow

Hwang, YuneSahng; Harshey, Rasika M.

doi:10.1128/mbio.00619-23

Cited by 5 publications

(3 citation statements)

References 68 publications

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“…Another phenotype that requires precise regulation of central metabolism in E. coli is biofilm formation. 50–52 In addition to controlling the switch between glycolysis and gluconeogenesis that occurs during biofilm formation, Cra directly activates the expression of the csgDEFG genes that are necessary to produce Curli, an attachment filament that is important for biofilm formation 53 . Indeed, a cra mutant strain is deficient in biofilm formation.…”

Section: Resultsmentioning

confidence: 99%

Fructose-1-kinase has pleiotropic roles inEscherichia coli

Weeramange,

Menjivar,

O’Neil

et al. 2023

Preprint

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InEscherichia coli, the master transcription regulator Catabolite Repressor Activator (Cra) regulates >100 genes in central metabolism. Cra binding to DNA is allosterically regulated by binding to fructose-1-phosphate (F-1-P), but the only documented source of F-1-P is from the concurrent import and phosphorylation of exogenous fructose. Thus, many have proposed that fructose-1,6-bisphosphate (F-1,6-BP) is also a physiological regulatory ligand. However, the role of F-1,6-BP has been widely debated. Here, we report that theE. colienzyme fructose-1-kinase (FruK) can carry out its “reverse” reaction under physiological substrate concentrations to generate F-1-P from F-1,6-BP. We further show that FruK directly binds Cra with nanomolar affinity and forms higher order, heterocomplexes. Growth assays with a ΔfruKstrain andfruKcomplementation show that FruK has a broader role in metabolism than fructose catabolism. The ΔfruKstrain also alters biofilm formation. SincefruKitself is repressed by Cra, these newly-reported events add layers to the dynamic regulation ofE. colicentral metabolism that occur in response to changing nutrients. These findings might have wide-spread relevance to other γ-proteobacteria, which conserve both Cra and FruK.

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Section: Resultsmentioning

confidence: 99%

Fructose-1-kinase has pleiotropic roles inEscherichia coli

Weeramange,

Menjivar,

O’Neil

et al. 2023

Preprint

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“…In bacteria, c‐di‐GMP is an intracellular nucleotide second messenger that controls a variety of cellular functions, including biofilm formation, cell cycle, and virulence 7 , 8 , 9 , 10 , 11 , 12 . c‐di‐GMP is a “switch molecule” that regulates the “lifestyle transition” from motility to biofilm 9 .…”

Section: The Global Regulation Of C‐di‐gmp In Bacteriamentioning

confidence: 99%

The global regulation of c‐di‐GMP and cAMP in bacteria

Liu,

Shi,

Jensen

et al. 2024

mLife

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Nucleotide second messengers are highly versatile signaling molecules that regulate a variety of key biological processes in bacteria. The best‐studied examples are cyclic AMP (cAMP) and bis‐(3′–5′)‐cyclic dimeric guanosine monophosphate (c‐di‐GMP), which both act as global regulators. Global regulatory frameworks of c‐di‐GMP and cAMP in bacteria show several parallels but also significant variances. In this review, we illustrate the global regulatory models of the two nucleotide second messengers, compare the different regulatory frameworks between c‐di‐GMP and cAMP, and discuss the mechanisms and physiological significance of cross‐regulation between c‐di‐GMP and cAMP. c‐di‐GMP responds to numerous signals dependent on a great number of metabolic enzymes, and it regulates various signal transduction pathways through its huge number of effectors with varying activities. In contrast, due to the limited quantity, the cAMP metabolic enzymes and its major effector are regulated at different levels by diverse signals. cAMP performs its global regulatory function primarily by controlling the transcription of a large number of genes via cAMP receptor protein (CRP) in most bacteria. This review can help us understand how bacteria use the two typical nucleotide second messengers to effectively coordinate and integrate various physiological processes, providing theoretical guidelines for future research.

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“…Furthermore, the environmental conditions under which distinct biofilms are formed can vary substantially even within a single isolate (Cole et al, 2014). Interference with other associated fundamental traits such as the cell cycle, recombination, and DNA repair and alteration in cell morphology seems to require specific cyclic di‐GMP turnover proteins (Fernandez et al, 2018; Gupta et al, 2016; Hwang & Harshey, 2023; Kaczmarczyk et al, 2020; Manikandan et al, 2018). This diversity of biofilm traits and their flexibility to respond to different environmental conditions partly answers the conundrum of the abundant presence of numerous cyclic di‐GMP turnover proteins encoded by bacterial genomes (Amikam & Galperin, 2006; López‐Ochoa et al, 2017; Lorite et al, 2022; Roelofs et al, 2015; Römling et al, 2005).…”

Section: Cyclic Di‐gmp As a Ubiquitous Lifestyle Regulator In Bacteriamentioning

confidence: 99%

Cyclic di‐GMP signaling—Where did you come from and where will you go?

Römling

2023

Molecular Microbiology

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Microbes including bacteria are required to respond to their often continuously changing ecological niches in order to survive. While many signaling molecules are produced as seemingly circumstantial byproducts of common biochemical reactions, there are a few second messenger signaling systems such as the ubiquitous cyclic di‐GMP second messenger system that arise through the synthesis of dedicated multidomain enzymes triggered by multiple diverse external and internal signals. Being one of the most numerous and widespread signaling system in bacteria, cyclic di‐GMP signaling contributes to adjust physiological and metabolic responses in all available ecological niches. Those niches range from deep‐sea and hydrothermal springs to the intracellular environment in human immune cells such as macrophages. This outmost adaptability is possible by the modularity of the cyclic di‐GMP turnover proteins which enables coupling of enzymatic activity to the diversity of sensory domains and the flexibility in cyclic di‐GMP binding sites. Nevertheless, commonly regulated fundamental microbial behavior include biofilm formation, motility, and acute and chronic virulence. The dedicated domains carrying out the enzymatic activity indicate an early evolutionary origin and diversification of “bona fide” second messengers such as cyclic di‐GMP which is estimated to have been present in the last universal common ancestor of archaea and bacteria and maintained in the bacterial kingdom until today. This perspective article addresses aspects of our current view on the cyclic di‐GMP signaling system and points to knowledge gaps that still await answers.

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A Second Role for the Second Messenger Cyclic-di-GMP in E. coli: Arresting Cell Growth by Altering Metabolic Flow

Cited by 5 publications

References 68 publications

Fructose-1-kinase has pleiotropic roles inEscherichia coli

Fructose-1-kinase has pleiotropic roles inEscherichia coli

The global regulation of c‐di‐GMP and cAMP in bacteria

Cyclic di‐GMP signaling—Where did you come from and where will you go?

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