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Francisella tularensis Exploits AMPK Activation to Harvest Host-Derived Nutrients Liberated from Host Lipolysis

Francisella tularensis is a zoonotic, facultative intracellular bacterial pathogen that replicates in a variety of cell types during infection. Following entry into the cell and phagosome escape, the bacterium replicates rapidly in the cytoplasm. F. tularensis intracellular growth depends on the ava...

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Autores principales: Dominguez, Sedelia R., Whiles, Shannon, Deobald, Kelly N., Kawula, Thomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9387300/
https://www.ncbi.nlm.nih.gov/pubmed/35916521
http://dx.doi.org/10.1128/iai.00155-22
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author Dominguez, Sedelia R.
Whiles, Shannon
Deobald, Kelly N.
Kawula, Thomas
author_facet Dominguez, Sedelia R.
Whiles, Shannon
Deobald, Kelly N.
Kawula, Thomas
author_sort Dominguez, Sedelia R.
collection PubMed
description Francisella tularensis is a zoonotic, facultative intracellular bacterial pathogen that replicates in a variety of cell types during infection. Following entry into the cell and phagosome escape, the bacterium replicates rapidly in the cytoplasm. F. tularensis intracellular growth depends on the availability of metabolizable essential nutrients to support replication. However, the mechanism by which metabolizable nutrients become available to the bacterium in the intracellular environment is not fully understood. We found that F. tularensis-infected cells had significantly smaller and fewer lipid droplets than uninfected cells. Inhibition of triacylglycerol degradation significantly reduced bacterial growth, whereas inhibition of triacylglycerol formation did not reduce bacterial growth, suggesting that triacylglycerols sequestered within lipid droplets are important nutrient sources for F. tularensis. We found that F. tularensis-infected cells had increased activation of lipolysis and the upstream regulatory protein AMP protein kinase (AMPK). These data suggest that F. tularensis exploits AMPK activation and lipid metabolism to use host-derived nutrients. Finally, we found that AMPK activation is correlated with an increased bacterial burden, which suggests that it is a host-mediated response to nutrient starvation that results from increased bacterial replication. Altogether, we conclude that F. tularensis exploits AMPK activation to access nutrients sequestered in lipid droplets, specifically glycerol and fatty acids, to undergo efficient bacterial replication and cause successful infection.
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spelling pubmed-93873002022-08-19 Francisella tularensis Exploits AMPK Activation to Harvest Host-Derived Nutrients Liberated from Host Lipolysis Dominguez, Sedelia R. Whiles, Shannon Deobald, Kelly N. Kawula, Thomas Infect Immun Cellular Microbiology: Pathogen-Host Cell Molecular Interactions Francisella tularensis is a zoonotic, facultative intracellular bacterial pathogen that replicates in a variety of cell types during infection. Following entry into the cell and phagosome escape, the bacterium replicates rapidly in the cytoplasm. F. tularensis intracellular growth depends on the availability of metabolizable essential nutrients to support replication. However, the mechanism by which metabolizable nutrients become available to the bacterium in the intracellular environment is not fully understood. We found that F. tularensis-infected cells had significantly smaller and fewer lipid droplets than uninfected cells. Inhibition of triacylglycerol degradation significantly reduced bacterial growth, whereas inhibition of triacylglycerol formation did not reduce bacterial growth, suggesting that triacylglycerols sequestered within lipid droplets are important nutrient sources for F. tularensis. We found that F. tularensis-infected cells had increased activation of lipolysis and the upstream regulatory protein AMP protein kinase (AMPK). These data suggest that F. tularensis exploits AMPK activation and lipid metabolism to use host-derived nutrients. Finally, we found that AMPK activation is correlated with an increased bacterial burden, which suggests that it is a host-mediated response to nutrient starvation that results from increased bacterial replication. Altogether, we conclude that F. tularensis exploits AMPK activation to access nutrients sequestered in lipid droplets, specifically glycerol and fatty acids, to undergo efficient bacterial replication and cause successful infection. American Society for Microbiology 2022-08-02 /pmc/articles/PMC9387300/ /pubmed/35916521 http://dx.doi.org/10.1128/iai.00155-22 Text en Copyright © 2022 Dominguez et al. 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 Cellular Microbiology: Pathogen-Host Cell Molecular Interactions
Dominguez, Sedelia R.
Whiles, Shannon
Deobald, Kelly N.
Kawula, Thomas
Francisella tularensis Exploits AMPK Activation to Harvest Host-Derived Nutrients Liberated from Host Lipolysis
title Francisella tularensis Exploits AMPK Activation to Harvest Host-Derived Nutrients Liberated from Host Lipolysis
title_full Francisella tularensis Exploits AMPK Activation to Harvest Host-Derived Nutrients Liberated from Host Lipolysis
title_fullStr Francisella tularensis Exploits AMPK Activation to Harvest Host-Derived Nutrients Liberated from Host Lipolysis
title_full_unstemmed Francisella tularensis Exploits AMPK Activation to Harvest Host-Derived Nutrients Liberated from Host Lipolysis
title_short Francisella tularensis Exploits AMPK Activation to Harvest Host-Derived Nutrients Liberated from Host Lipolysis
title_sort francisella tularensis exploits ampk activation to harvest host-derived nutrients liberated from host lipolysis
topic Cellular Microbiology: Pathogen-Host Cell Molecular Interactions
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9387300/
https://www.ncbi.nlm.nih.gov/pubmed/35916521
http://dx.doi.org/10.1128/iai.00155-22
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