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Structure, Dynamics and Cellular Insight Into Novel Substrates of the Legionella pneumophila Type II Secretion System

Legionella pneumophila is a Gram-negative bacterium that is able to replicate within a broad range of aquatic protozoan hosts. L. pneumophila is also an opportunistic human pathogen that can infect macrophages and epithelia in the lung and lead to Legionnaires’ disease. The type II secretion system...

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Autores principales: Portlock, Theo J., Tyson, Jessica Y., Dantu, Sarath C., Rehman, Saima, White, Richard C., McIntire, Ian E., Sewell, Lee, Richardson, Katherine, Shaw, Rosie, Pandini, Alessandro, Cianciotto, Nicholas P., Garnett, James A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325957/
https://www.ncbi.nlm.nih.gov/pubmed/32656228
http://dx.doi.org/10.3389/fmolb.2020.00112
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author Portlock, Theo J.
Tyson, Jessica Y.
Dantu, Sarath C.
Rehman, Saima
White, Richard C.
McIntire, Ian E.
Sewell, Lee
Richardson, Katherine
Shaw, Rosie
Pandini, Alessandro
Cianciotto, Nicholas P.
Garnett, James A.
author_facet Portlock, Theo J.
Tyson, Jessica Y.
Dantu, Sarath C.
Rehman, Saima
White, Richard C.
McIntire, Ian E.
Sewell, Lee
Richardson, Katherine
Shaw, Rosie
Pandini, Alessandro
Cianciotto, Nicholas P.
Garnett, James A.
author_sort Portlock, Theo J.
collection PubMed
description Legionella pneumophila is a Gram-negative bacterium that is able to replicate within a broad range of aquatic protozoan hosts. L. pneumophila is also an opportunistic human pathogen that can infect macrophages and epithelia in the lung and lead to Legionnaires’ disease. The type II secretion system is a key virulence factor of L. pneumophila and is used to promote bacterial growth at low temperatures, regulate biofilm formation, modulate host responses to infection, facilitate bacterial penetration of mucin gels and is necessary for intracellular growth during the initial stages of infection. The L. pneumophila type II secretion system exports at least 25 substrates out of the bacterium and several of these, including NttA to NttG, contain unique amino acid sequences that are generally not observed outside of the Legionella genus. NttA, NttC, and NttD are required for infection of several amoebal species but it is unclear what influence other novel substrates have within their host. In this study, we show that NttE is required for optimal infection of Acanthamoeba castellanii and Vermamoeba vermiformis amoeba and is essential for the typical colony morphology of L. pneumophila. In addition, we report the atomic structures of NttA, NttC, and NttE and through a combined biophysical and biochemical hypothesis driven approach we propose novel functions for these substrates during infection. This work lays the foundation for future studies into the mechanistic understanding of novel type II substrate functions and how these relate to L. pneumophila ecology and disease.
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spelling pubmed-73259572020-07-09 Structure, Dynamics and Cellular Insight Into Novel Substrates of the Legionella pneumophila Type II Secretion System Portlock, Theo J. Tyson, Jessica Y. Dantu, Sarath C. Rehman, Saima White, Richard C. McIntire, Ian E. Sewell, Lee Richardson, Katherine Shaw, Rosie Pandini, Alessandro Cianciotto, Nicholas P. Garnett, James A. Front Mol Biosci Molecular Biosciences Legionella pneumophila is a Gram-negative bacterium that is able to replicate within a broad range of aquatic protozoan hosts. L. pneumophila is also an opportunistic human pathogen that can infect macrophages and epithelia in the lung and lead to Legionnaires’ disease. The type II secretion system is a key virulence factor of L. pneumophila and is used to promote bacterial growth at low temperatures, regulate biofilm formation, modulate host responses to infection, facilitate bacterial penetration of mucin gels and is necessary for intracellular growth during the initial stages of infection. The L. pneumophila type II secretion system exports at least 25 substrates out of the bacterium and several of these, including NttA to NttG, contain unique amino acid sequences that are generally not observed outside of the Legionella genus. NttA, NttC, and NttD are required for infection of several amoebal species but it is unclear what influence other novel substrates have within their host. In this study, we show that NttE is required for optimal infection of Acanthamoeba castellanii and Vermamoeba vermiformis amoeba and is essential for the typical colony morphology of L. pneumophila. In addition, we report the atomic structures of NttA, NttC, and NttE and through a combined biophysical and biochemical hypothesis driven approach we propose novel functions for these substrates during infection. This work lays the foundation for future studies into the mechanistic understanding of novel type II substrate functions and how these relate to L. pneumophila ecology and disease. Frontiers Media S.A. 2020-06-11 /pmc/articles/PMC7325957/ /pubmed/32656228 http://dx.doi.org/10.3389/fmolb.2020.00112 Text en Copyright © 2020 Portlock, Tyson, Dantu, Rehman, White, McIntire, Sewell, Richardson, Shaw, Pandini, Cianciotto and Garnett. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Biosciences
Portlock, Theo J.
Tyson, Jessica Y.
Dantu, Sarath C.
Rehman, Saima
White, Richard C.
McIntire, Ian E.
Sewell, Lee
Richardson, Katherine
Shaw, Rosie
Pandini, Alessandro
Cianciotto, Nicholas P.
Garnett, James A.
Structure, Dynamics and Cellular Insight Into Novel Substrates of the Legionella pneumophila Type II Secretion System
title Structure, Dynamics and Cellular Insight Into Novel Substrates of the Legionella pneumophila Type II Secretion System
title_full Structure, Dynamics and Cellular Insight Into Novel Substrates of the Legionella pneumophila Type II Secretion System
title_fullStr Structure, Dynamics and Cellular Insight Into Novel Substrates of the Legionella pneumophila Type II Secretion System
title_full_unstemmed Structure, Dynamics and Cellular Insight Into Novel Substrates of the Legionella pneumophila Type II Secretion System
title_short Structure, Dynamics and Cellular Insight Into Novel Substrates of the Legionella pneumophila Type II Secretion System
title_sort structure, dynamics and cellular insight into novel substrates of the legionella pneumophila type ii secretion system
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325957/
https://www.ncbi.nlm.nih.gov/pubmed/32656228
http://dx.doi.org/10.3389/fmolb.2020.00112
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