Human Serum Albumin Binds Streptolysin O (SLO) Toxin Produced by Group A Streptococcus and Inhibits Its Cytotoxic and Hemolytic Effects
The pathogenicity of group A Streptococcus (GAS) is mediated by direct bacterial invasivity and toxin-associated damage. Among the extracellular products, the exotoxin streptolysin O (SLO) is produced by almost all GAS strains. SLO is a pore forming toxin (PFT) hemolitically active and extremely tox...
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doaj-dd379f22f44148558eba8555bb116cc02020-12-08T04:42:18ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-12-011110.3389/fimmu.2020.507092507092Human Serum Albumin Binds Streptolysin O (SLO) Toxin Produced by Group A Streptococcus and Inhibits Its Cytotoxic and Hemolytic EffectsGian Marco Vita0Giovanna De Simone1Loris Leboffe2Francesca Montagnani3Francesca Montagnani4Davide Mariotti5Stefano Di Bella6Roberto Luzzati7Andrea Gori8Paolo Ascenzi9Alessandra di Masi10Department of Sciences, Roma Tre University, Roma, ItalyDepartment of Sciences, Roma Tre University, Roma, ItalyDepartment of Sciences, Roma Tre University, Roma, ItalyDepartment of Medical Biotechnologies, University of Siena, Siena, ItalyInfectious and Tropical Diseases Unit, Department of Medical Sciences, Hospital of Siena, Siena, ItalyDepartment of Sciences, Roma Tre University, Roma, ItalyInfectious Diseases Unit, Clinical Department of Medical, Siurgical, and Health Sciences, University of Trieste, Trieste, ItalyInfectious Diseases Unit, Clinical Department of Medical, Siurgical, and Health Sciences, University of Trieste, Trieste, ItalyInfectious Diseases Unit, Department of Internal Medicine, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Centre for Multidisciplinary Research in Health Science (MACH), University of Milan, Milan, ItalyDepartment of Sciences, Roma Tre University, Roma, ItalyDepartment of Sciences, Roma Tre University, Roma, ItalyThe pathogenicity of group A Streptococcus (GAS) is mediated by direct bacterial invasivity and toxin-associated damage. Among the extracellular products, the exotoxin streptolysin O (SLO) is produced by almost all GAS strains. SLO is a pore forming toxin (PFT) hemolitically active and extremely toxic in vivo. Recent evidence suggests that human serum albumin (HSA), the most abundant protein in plasma, is a player in the innate immunity “orchestra.” We previously demonstrated that HSA acts as a physiological buffer, partially neutralizing Clostridioides difficile toxins that reach the bloodstream after being produced in the colon. Here, we report the in vitro and ex vivo capability of HSA to neutralize the cytotoxic and hemolytic effects of SLO. HSA binds SLO with high affinity at a non-conventional site located in domain II, which was previously reported to interact also with C. difficile toxins. HSA:SLO recognition protects HEp-2 and A549 cells from cytotoxic effects and cell membrane permeabilization induced by SLO. Moreover, HSA inhibits the SLO-dependent hemolytic effect in red blood cells isolated from healthy human donors. The recognition of SLO by HSA may have a significant protective role in human serum and sustains the emerging hypothesis that HSA is an important constituent of the innate immunity system.https://www.frontiersin.org/articles/10.3389/fimmu.2020.507092/fullhuman serum albuminred blood cellsstreptolysin OStreptococcus pyogenestoxin |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Gian Marco Vita Giovanna De Simone Loris Leboffe Francesca Montagnani Francesca Montagnani Davide Mariotti Stefano Di Bella Roberto Luzzati Andrea Gori Paolo Ascenzi Alessandra di Masi |
spellingShingle |
Gian Marco Vita Giovanna De Simone Loris Leboffe Francesca Montagnani Francesca Montagnani Davide Mariotti Stefano Di Bella Roberto Luzzati Andrea Gori Paolo Ascenzi Alessandra di Masi Human Serum Albumin Binds Streptolysin O (SLO) Toxin Produced by Group A Streptococcus and Inhibits Its Cytotoxic and Hemolytic Effects Frontiers in Immunology human serum albumin red blood cells streptolysin O Streptococcus pyogenes toxin |
author_facet |
Gian Marco Vita Giovanna De Simone Loris Leboffe Francesca Montagnani Francesca Montagnani Davide Mariotti Stefano Di Bella Roberto Luzzati Andrea Gori Paolo Ascenzi Alessandra di Masi |
author_sort |
Gian Marco Vita |
title |
Human Serum Albumin Binds Streptolysin O (SLO) Toxin Produced by Group A Streptococcus and Inhibits Its Cytotoxic and Hemolytic Effects |
title_short |
Human Serum Albumin Binds Streptolysin O (SLO) Toxin Produced by Group A Streptococcus and Inhibits Its Cytotoxic and Hemolytic Effects |
title_full |
Human Serum Albumin Binds Streptolysin O (SLO) Toxin Produced by Group A Streptococcus and Inhibits Its Cytotoxic and Hemolytic Effects |
title_fullStr |
Human Serum Albumin Binds Streptolysin O (SLO) Toxin Produced by Group A Streptococcus and Inhibits Its Cytotoxic and Hemolytic Effects |
title_full_unstemmed |
Human Serum Albumin Binds Streptolysin O (SLO) Toxin Produced by Group A Streptococcus and Inhibits Its Cytotoxic and Hemolytic Effects |
title_sort |
human serum albumin binds streptolysin o (slo) toxin produced by group a streptococcus and inhibits its cytotoxic and hemolytic effects |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2020-12-01 |
description |
The pathogenicity of group A Streptococcus (GAS) is mediated by direct bacterial invasivity and toxin-associated damage. Among the extracellular products, the exotoxin streptolysin O (SLO) is produced by almost all GAS strains. SLO is a pore forming toxin (PFT) hemolitically active and extremely toxic in vivo. Recent evidence suggests that human serum albumin (HSA), the most abundant protein in plasma, is a player in the innate immunity “orchestra.” We previously demonstrated that HSA acts as a physiological buffer, partially neutralizing Clostridioides difficile toxins that reach the bloodstream after being produced in the colon. Here, we report the in vitro and ex vivo capability of HSA to neutralize the cytotoxic and hemolytic effects of SLO. HSA binds SLO with high affinity at a non-conventional site located in domain II, which was previously reported to interact also with C. difficile toxins. HSA:SLO recognition protects HEp-2 and A549 cells from cytotoxic effects and cell membrane permeabilization induced by SLO. Moreover, HSA inhibits the SLO-dependent hemolytic effect in red blood cells isolated from healthy human donors. The recognition of SLO by HSA may have a significant protective role in human serum and sustains the emerging hypothesis that HSA is an important constituent of the innate immunity system. |
topic |
human serum albumin red blood cells streptolysin O Streptococcus pyogenes toxin |
url |
https://www.frontiersin.org/articles/10.3389/fimmu.2020.507092/full |
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