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A Second Role for the Second Messenger Cyclic-di-GMP in E. coli: Arresting Cell Growth by Altering Metabolic Flow
c-di-GMP primarily controls motile to sessile transitions in bacteria. Diguanylate cyclases (DGCs) catalyze the synthesis of c-di-GMP from two GTP molecules. Typically, bacteria encode multiple DGCs that are activated by specific environmental signals. Their catalytic activity is modulated by c-di-G...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10127611/ https://www.ncbi.nlm.nih.gov/pubmed/37036337 http://dx.doi.org/10.1128/mbio.00619-23 |
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author | Hwang, YuneSahng Harshey, Rasika M. |
author_facet | Hwang, YuneSahng Harshey, Rasika M. |
author_sort | Hwang, YuneSahng |
collection | PubMed |
description | c-di-GMP primarily controls motile to sessile transitions in bacteria. Diguanylate cyclases (DGCs) catalyze the synthesis of c-di-GMP from two GTP molecules. Typically, bacteria encode multiple DGCs that are activated by specific environmental signals. Their catalytic activity is modulated by c-di-GMP binding to autoinhibitory sites (I-sites). YfiN is a conserved inner membrane DGC that lacks these sites. Instead, YfiN activity is directly repressed by periplasmic YfiR, which is inactivated by redox stress. In Escherichia coli, an additional envelope stress causes YfiN to relocate to the mid-cell to inhibit cell division by interacting with the division machinery. Here, we report a third activity for YfiN in E. coli, where cell growth is inhibited without YfiN relocating to the division site. This action of YfiN is only observed when the bacteria are cultured on gluconeogenic carbon sources, and is dependent on absence of the autoinhibitory sites. Restoration of I-site function relieves the growth-arrest phenotype, and disabling this function in a heterologous DGC causes acquisition of this phenotype. Arrested cells are tolerant to a wide range of antibiotics. We show that the likely cause of growth arrest is depletion of cellular GTP from run-away synthesis of c-di-GMP, explaining the dependence of growth arrest on gluconeogenic carbon sources that exhaust more GTP during production of glucose. This is the first report of c-di-GMP-mediated growth arrest by altering metabolic flow. |
format | Online Article Text |
id | pubmed-10127611 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-101276112023-04-26 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. mBio Research Article c-di-GMP primarily controls motile to sessile transitions in bacteria. Diguanylate cyclases (DGCs) catalyze the synthesis of c-di-GMP from two GTP molecules. Typically, bacteria encode multiple DGCs that are activated by specific environmental signals. Their catalytic activity is modulated by c-di-GMP binding to autoinhibitory sites (I-sites). YfiN is a conserved inner membrane DGC that lacks these sites. Instead, YfiN activity is directly repressed by periplasmic YfiR, which is inactivated by redox stress. In Escherichia coli, an additional envelope stress causes YfiN to relocate to the mid-cell to inhibit cell division by interacting with the division machinery. Here, we report a third activity for YfiN in E. coli, where cell growth is inhibited without YfiN relocating to the division site. This action of YfiN is only observed when the bacteria are cultured on gluconeogenic carbon sources, and is dependent on absence of the autoinhibitory sites. Restoration of I-site function relieves the growth-arrest phenotype, and disabling this function in a heterologous DGC causes acquisition of this phenotype. Arrested cells are tolerant to a wide range of antibiotics. We show that the likely cause of growth arrest is depletion of cellular GTP from run-away synthesis of c-di-GMP, explaining the dependence of growth arrest on gluconeogenic carbon sources that exhaust more GTP during production of glucose. This is the first report of c-di-GMP-mediated growth arrest by altering metabolic flow. American Society for Microbiology 2023-04-10 /pmc/articles/PMC10127611/ /pubmed/37036337 http://dx.doi.org/10.1128/mbio.00619-23 Text en Copyright © 2023 Hwang and Harshey. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Hwang, YuneSahng Harshey, Rasika M. A Second Role for the Second Messenger Cyclic-di-GMP in E. coli: Arresting Cell Growth by Altering Metabolic Flow |
title | A Second Role for the Second Messenger Cyclic-di-GMP in E. coli: Arresting Cell Growth by Altering Metabolic Flow |
title_full | A Second Role for the Second Messenger Cyclic-di-GMP in E. coli: Arresting Cell Growth by Altering Metabolic Flow |
title_fullStr | A Second Role for the Second Messenger Cyclic-di-GMP in E. coli: Arresting Cell Growth by Altering Metabolic Flow |
title_full_unstemmed | A Second Role for the Second Messenger Cyclic-di-GMP in E. coli: Arresting Cell Growth by Altering Metabolic Flow |
title_short | A Second Role for the Second Messenger Cyclic-di-GMP in E. coli: Arresting Cell Growth by Altering Metabolic Flow |
title_sort | second role for the second messenger cyclic-di-gmp in e. coli: arresting cell growth by altering metabolic flow |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10127611/ https://www.ncbi.nlm.nih.gov/pubmed/37036337 http://dx.doi.org/10.1128/mbio.00619-23 |
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