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Peptidoglycan deacetylation controls type IV secretion and the intracellular survival of the bacterial pathogen Legionella pneumophila

Peptidoglycan is a critical component of the bacteria cell envelope. Remodeling of the peptidoglycan is required for numerous essential cellular processes and has been linked to bacterial pathogenesis. Peptidoglycan deacetylases that remove the acetyl group of the N-acetylglucosamine (NAG) subunit p...

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Autores principales: Boamah, David, Gilmore, Michael C., Bourget, Sarah, Ghosh, Anushka, Hossain, Mohammad J., Vogel, Joseph P., Cava, Felipe, O’Connor, Tamara J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10266036/
https://www.ncbi.nlm.nih.gov/pubmed/37252954
http://dx.doi.org/10.1073/pnas.2119658120
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author Boamah, David
Gilmore, Michael C.
Bourget, Sarah
Ghosh, Anushka
Hossain, Mohammad J.
Vogel, Joseph P.
Cava, Felipe
O’Connor, Tamara J.
author_facet Boamah, David
Gilmore, Michael C.
Bourget, Sarah
Ghosh, Anushka
Hossain, Mohammad J.
Vogel, Joseph P.
Cava, Felipe
O’Connor, Tamara J.
author_sort Boamah, David
collection PubMed
description Peptidoglycan is a critical component of the bacteria cell envelope. Remodeling of the peptidoglycan is required for numerous essential cellular processes and has been linked to bacterial pathogenesis. Peptidoglycan deacetylases that remove the acetyl group of the N-acetylglucosamine (NAG) subunit protect bacterial pathogens from immune recognition and digestive enzymes secreted at the site of infection. However, the full extent of this modification on bacterial physiology and pathogenesis is not known. Here, we identify a polysaccharide deacetylase of the intracellular bacterial pathogen Legionella pneumophila and define a two-tiered role for this enzyme in Legionella pathogenesis. First, NAG deacetylation is important for the proper localization and function of the Type IVb secretion system, linking peptidoglycan editing to the modulation of host cellular processes through the action of secreted virulence factors. As a consequence, the Legionella vacuole mis-traffics along the endocytic pathway to the lysosome, preventing the formation of a replication permissive compartment. Second, within the lysosome, the inability to deacetylate the peptidoglycan renders the bacteria more sensitive to lysozyme-mediated degradation, resulting in increased bacterial death. Thus, the ability to deacetylate NAG is important for bacteria to persist within host cells and in turn, Legionella virulence. Collectively, these results expand the function of peptidoglycan deacetylases in bacteria, linking peptidoglycan editing, Type IV secretion, and the intracellular fate of a bacterial pathogen.
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spelling pubmed-102660362023-11-30 Peptidoglycan deacetylation controls type IV secretion and the intracellular survival of the bacterial pathogen Legionella pneumophila Boamah, David Gilmore, Michael C. Bourget, Sarah Ghosh, Anushka Hossain, Mohammad J. Vogel, Joseph P. Cava, Felipe O’Connor, Tamara J. Proc Natl Acad Sci U S A Biological Sciences Peptidoglycan is a critical component of the bacteria cell envelope. Remodeling of the peptidoglycan is required for numerous essential cellular processes and has been linked to bacterial pathogenesis. Peptidoglycan deacetylases that remove the acetyl group of the N-acetylglucosamine (NAG) subunit protect bacterial pathogens from immune recognition and digestive enzymes secreted at the site of infection. However, the full extent of this modification on bacterial physiology and pathogenesis is not known. Here, we identify a polysaccharide deacetylase of the intracellular bacterial pathogen Legionella pneumophila and define a two-tiered role for this enzyme in Legionella pathogenesis. First, NAG deacetylation is important for the proper localization and function of the Type IVb secretion system, linking peptidoglycan editing to the modulation of host cellular processes through the action of secreted virulence factors. As a consequence, the Legionella vacuole mis-traffics along the endocytic pathway to the lysosome, preventing the formation of a replication permissive compartment. Second, within the lysosome, the inability to deacetylate the peptidoglycan renders the bacteria more sensitive to lysozyme-mediated degradation, resulting in increased bacterial death. Thus, the ability to deacetylate NAG is important for bacteria to persist within host cells and in turn, Legionella virulence. Collectively, these results expand the function of peptidoglycan deacetylases in bacteria, linking peptidoglycan editing, Type IV secretion, and the intracellular fate of a bacterial pathogen. National Academy of Sciences 2023-05-30 2023-06-06 /pmc/articles/PMC10266036/ /pubmed/37252954 http://dx.doi.org/10.1073/pnas.2119658120 Text en Copyright © 2023 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Biological Sciences
Boamah, David
Gilmore, Michael C.
Bourget, Sarah
Ghosh, Anushka
Hossain, Mohammad J.
Vogel, Joseph P.
Cava, Felipe
O’Connor, Tamara J.
Peptidoglycan deacetylation controls type IV secretion and the intracellular survival of the bacterial pathogen Legionella pneumophila
title Peptidoglycan deacetylation controls type IV secretion and the intracellular survival of the bacterial pathogen Legionella pneumophila
title_full Peptidoglycan deacetylation controls type IV secretion and the intracellular survival of the bacterial pathogen Legionella pneumophila
title_fullStr Peptidoglycan deacetylation controls type IV secretion and the intracellular survival of the bacterial pathogen Legionella pneumophila
title_full_unstemmed Peptidoglycan deacetylation controls type IV secretion and the intracellular survival of the bacterial pathogen Legionella pneumophila
title_short Peptidoglycan deacetylation controls type IV secretion and the intracellular survival of the bacterial pathogen Legionella pneumophila
title_sort peptidoglycan deacetylation controls type iv secretion and the intracellular survival of the bacterial pathogen legionella pneumophila
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10266036/
https://www.ncbi.nlm.nih.gov/pubmed/37252954
http://dx.doi.org/10.1073/pnas.2119658120
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