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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752801/ https://www.ncbi.nlm.nih.gov/pubmed/33363530 http://dx.doi.org/10.3389/fimmu.2020.507092 |
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author | Vita, Gian Marco De Simone, Giovanna Leboffe, Loris Montagnani, Francesca Mariotti, Davide Di Bella, Stefano Luzzati, Roberto Gori, Andrea Ascenzi, Paolo di Masi, Alessandra |
author_facet | Vita, Gian Marco De Simone, Giovanna Leboffe, Loris Montagnani, Francesca Mariotti, Davide Di Bella, Stefano Luzzati, Roberto Gori, Andrea Ascenzi, Paolo di Masi, Alessandra |
author_sort | Vita, Gian Marco |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-7752801 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-77528012020-12-23 Human Serum Albumin Binds Streptolysin O (SLO) Toxin Produced by Group A Streptococcus and Inhibits Its Cytotoxic and Hemolytic Effects Vita, Gian Marco De Simone, Giovanna Leboffe, Loris Montagnani, Francesca Mariotti, Davide Di Bella, Stefano Luzzati, Roberto Gori, Andrea Ascenzi, Paolo di Masi, Alessandra Front Immunol Immunology 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. Frontiers Media S.A. 2020-12-08 /pmc/articles/PMC7752801/ /pubmed/33363530 http://dx.doi.org/10.3389/fimmu.2020.507092 Text en Copyright © 2020 Vita, De Simone, Leboffe, Montagnani, Mariotti, Di Bella, Luzzati, Gori, Ascenzi and di Masi 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 | Immunology Vita, Gian Marco De Simone, Giovanna Leboffe, Loris Montagnani, Francesca Mariotti, Davide Di Bella, Stefano Luzzati, Roberto Gori, Andrea Ascenzi, Paolo di Masi, Alessandra Human Serum Albumin Binds Streptolysin O (SLO) Toxin Produced by Group A Streptococcus and Inhibits Its Cytotoxic and Hemolytic Effects |
title | 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_short | 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 |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752801/ https://www.ncbi.nlm.nih.gov/pubmed/33363530 http://dx.doi.org/10.3389/fimmu.2020.507092 |
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