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

• Published in: PloS one Vol. 15; no. 3; p. e0219275
• Main Authors: Turner, Matthew L, Owens, Sian E, Sheldon, I Martin
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 12-03-2020; Public Library of Science (PLoS)
• Subjects: Amino acids; Animals; Bacteria; Bacterial diseases; Bacterial infections; Bacterial Proteins - toxicity; Bacterial Toxins - toxicity; Biology and Life Sciences; Cattle; Cell growth; Cell membranes; Cell viability; Cholesterol; Cholesterol - metabolism; Cytolysins; Cytoprotection - drug effects; Cytotoxins - toxicity; Damage; Dehydrogenase; Dehydrogenases; Deoxyribonucleic acid; Deprivation; DNA; Epithelial cells; Glutamine; Glutamine - pharmacology; Health aspects; HeLa Cells; Hemolysin Proteins - toxicity; Humans; Hypotheses; Immune system; Infection; Infections; Krebs cycle; L-Lactate dehydrogenase; L-Lactate Dehydrogenase - metabolism; Lactate dehydrogenase; Lactic acid; Leakage; Life sciences; Medicine and Health Sciences; Membranes; Metabolism; Pathogens; Physical Sciences; Physiological aspects; Pore formation; Potassium; Pyolysin; Regulators; Research and analysis methods; Scientific equipment industry; Streptolysins - toxicity; Stromal cells; Stromal Cells - drug effects; Tissues; TOR protein; Toxins; Tricarboxylic acid cycle; United States; United Kingdom; United Kingdom > UK; Wales
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0219275

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.