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Glutamine supports the protection of tissue cells against the damage caused by cholesterol-dependent cytolysins from pathogenic bacteria

Matthew Turner Orcid Logo, Sian-eleri Owens Orcid Logo, Martin Sheldon Orcid Logo

PLOS ONE, Volume: 15, Issue: 3, Start page: e0219275

Swansea University Authors: Matthew Turner Orcid Logo, Sian-eleri Owens Orcid Logo, Martin Sheldon Orcid Logo

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DOI (Published version): 10.1371/journal.pone.0219275

Abstract

Pathogenic bacteria often damage tissues by secreting toxins that form pores in cell membranes, and the most common pore-forming toxins are cholesterol-dependent cytolysins. During bacterial infections, glutamine becomes a conditionally essential amino acid, and glutamine is an important nutrient fo...

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Published in: PLOS ONE
ISSN: 1932-6203
Published: Public Library of Science (PLoS) 2020
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spelling 2020-07-05T12:00:35.1144166 v2 53816 2020-03-12 Glutamine supports the protection of tissue cells against the damage caused by cholesterol-dependent cytolysins from pathogenic bacteria d6ee69e43774ed1124d27923140b1e0b 0000-0002-1369-4051 Matthew Turner Matthew Turner true false 721deb4604d122019244cfdf08820cbe 0000-0003-1806-5235 Sian-eleri Owens Sian-eleri Owens true false ab0f74b794e59cc270c69e63ee1d9748 0000-0001-7902-5558 Martin Sheldon Martin Sheldon true false 2020-03-12 PMSC Pathogenic bacteria often damage tissues by secreting toxins that form pores in cell membranes, and the most common pore-forming toxins are cholesterol-dependent cytolysins. During bacterial infections, glutamine becomes a conditionally essential amino acid, and glutamine is an important nutrient for immune cells. However, the role of glutamine in protecting tissue cells against pore-forming toxins is unclear. Here we tested the hypothesis that glutamine supports the protection of tissue cells against the damage caused by cholesterol-dependent cytolysins. Stromal and epithelial cells were sensitive to damage by the cholesterol-dependent cytolysins, pyolysin and streptolysin O, as determined by leakage of potassium and lactate dehydrogenase from cells, and reduced cell viability. However, glutamine deprivation increased the leakage of lactate dehydrogenase and reduced the viability of cells challenged with cholesterol-dependent cytolysins. Without glutamine, stromal cells challenged with pyolysin leaked lactate dehydrogenase (control vs. pyolysin, 2.6 ± 0.6 vs. 34.4 ± 4.5 AU, n = 12), which was more than three-fold the leakage from cells supplied with 2 mM glutamine (control vs. pyolysin, 2.2 ± 0.3 vs. 9.4 ± 1.0 AU). Glutamine cytoprotection did not depend on glutaminolysis, replenishing the Krebs cycle via succinate, changes in cellular cholesterol, or regulators of cell metabolism (AMPK and mTOR). In conclusion, although the mechanism remains elusive, we found that glutamine supports the protection of tissue cells against the damage caused by cholesterol-dependent cytolysins from pathogenic bacteria. Journal Article PLOS ONE 15 3 e0219275 Public Library of Science (PLoS) 1932-6203 12 3 2020 2020-03-12 10.1371/journal.pone.0219275 COLLEGE NANME Medicine COLLEGE CODE PMSC Swansea University UKRI, BBSRC, BB/K006592/1 2020-07-05T12:00:35.1144166 2020-03-12T20:34:19.0517229 Matthew Turner 0000-0002-1369-4051 1 Sian-eleri Owens 0000-0003-1806-5235 2 Martin Sheldon 0000-0001-7902-5558 3 53816__16845__63a5abc7c75b402f92f0be591b8772ef.pdf journal.pone.0219275.pdf 2020-03-12T20:37:39.3928819 Output 2688266 application/pdf Version of Record true Released under the terms of a Creative Commons Attribution License (CC-BY). true eng http://creativecommons.org/licenses/by/4.0/
title Glutamine supports the protection of tissue cells against the damage caused by cholesterol-dependent cytolysins from pathogenic bacteria
spellingShingle Glutamine supports the protection of tissue cells against the damage caused by cholesterol-dependent cytolysins from pathogenic bacteria
Matthew Turner
Sian-eleri Owens
Martin Sheldon
title_short Glutamine supports the protection of tissue cells against the damage caused by cholesterol-dependent cytolysins from pathogenic bacteria
title_full Glutamine supports the protection of tissue cells against the damage caused by cholesterol-dependent cytolysins from pathogenic bacteria
title_fullStr Glutamine supports the protection of tissue cells against the damage caused by cholesterol-dependent cytolysins from pathogenic bacteria
title_full_unstemmed Glutamine supports the protection of tissue cells against the damage caused by cholesterol-dependent cytolysins from pathogenic bacteria
title_sort Glutamine supports the protection of tissue cells against the damage caused by cholesterol-dependent cytolysins from pathogenic bacteria
author_id_str_mv d6ee69e43774ed1124d27923140b1e0b
721deb4604d122019244cfdf08820cbe
ab0f74b794e59cc270c69e63ee1d9748
author_id_fullname_str_mv d6ee69e43774ed1124d27923140b1e0b_***_Matthew Turner
721deb4604d122019244cfdf08820cbe_***_Sian-eleri Owens
ab0f74b794e59cc270c69e63ee1d9748_***_Martin Sheldon
author Matthew Turner
Sian-eleri Owens
Martin Sheldon
author2 Matthew Turner
Sian-eleri Owens
Martin Sheldon
format Journal article
container_title PLOS ONE
container_volume 15
container_issue 3
container_start_page e0219275
publishDate 2020
institution Swansea University
issn 1932-6203
doi_str_mv 10.1371/journal.pone.0219275
publisher Public Library of Science (PLoS)
document_store_str 1
active_str 0
description Pathogenic bacteria often damage tissues by secreting toxins that form pores in cell membranes, and the most common pore-forming toxins are cholesterol-dependent cytolysins. During bacterial infections, glutamine becomes a conditionally essential amino acid, and glutamine is an important nutrient for immune cells. However, the role of glutamine in protecting tissue cells against pore-forming toxins is unclear. Here we tested the hypothesis that glutamine supports the protection of tissue cells against the damage caused by cholesterol-dependent cytolysins. Stromal and epithelial cells were sensitive to damage by the cholesterol-dependent cytolysins, pyolysin and streptolysin O, as determined by leakage of potassium and lactate dehydrogenase from cells, and reduced cell viability. However, glutamine deprivation increased the leakage of lactate dehydrogenase and reduced the viability of cells challenged with cholesterol-dependent cytolysins. Without glutamine, stromal cells challenged with pyolysin leaked lactate dehydrogenase (control vs. pyolysin, 2.6 ± 0.6 vs. 34.4 ± 4.5 AU, n = 12), which was more than three-fold the leakage from cells supplied with 2 mM glutamine (control vs. pyolysin, 2.2 ± 0.3 vs. 9.4 ± 1.0 AU). Glutamine cytoprotection did not depend on glutaminolysis, replenishing the Krebs cycle via succinate, changes in cellular cholesterol, or regulators of cell metabolism (AMPK and mTOR). In conclusion, although the mechanism remains elusive, we found that glutamine supports the protection of tissue cells against the damage caused by cholesterol-dependent cytolysins from pathogenic bacteria.
published_date 2020-03-12T04:06:58Z
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