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Oxidation of bacillithiol during killing of Staphylococcus aureus USA300 inside neutrophil phagosomes
Targeting immune evasion tactics of pathogenic bacteria may hold the key to treating recalcitrant bacterial infections. Staphylococcus aureus produces bacillithiol (BSH), its major low‐molecular‐weight thiol, which is thought to protect this opportunistic human pathogen against the bombardment of ox...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9796752/ https://www.ncbi.nlm.nih.gov/pubmed/35621076 http://dx.doi.org/10.1002/JLB.4HI1021-538RR |
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author | Ashby, Louisa V Springer, Reuben Loi, Vu Van Antelmann, Haike Hampton, Mark B Kettle, Anthony J Dickerhof, Nina |
author_facet | Ashby, Louisa V Springer, Reuben Loi, Vu Van Antelmann, Haike Hampton, Mark B Kettle, Anthony J Dickerhof, Nina |
author_sort | Ashby, Louisa V |
collection | PubMed |
description | Targeting immune evasion tactics of pathogenic bacteria may hold the key to treating recalcitrant bacterial infections. Staphylococcus aureus produces bacillithiol (BSH), its major low‐molecular‐weight thiol, which is thought to protect this opportunistic human pathogen against the bombardment of oxidants inside neutrophil phagosomes. Here, we show that BSH was oxidized when human neutrophils phagocytosed S. aureus, but provided limited protection to the bacteria. We used mass spectrometry to measure the oxidation of BSH upon exposure of S. aureus USA300 to either a bolus of hypochlorous acid (HOCl) or a flux generated by the neutrophil enzyme myeloperoxidase. Oxidation of BSH and loss of bacterial viability were strongly correlated (r = 0.99, p < 0.001). BSH was fully oxidized after exposure of S. aureus to lethal doses of HOCl. However, there was no relationship between the initial BSH levels and the dose of HOCl required for bacterial killing. In contrast to the HOCl systems, only 50% of total BSH was oxidized when neutrophils killed the majority of phagocytosed bacteria. Oxidation of BSH was decreased upon inhibition of myeloperoxidase, implicating HOCl in phagosomal BSH oxidation. A BSH‐deficient S. aureus USA300 mutant was slightly more susceptible to treatment with either HOCl or ammonia chloramine, or to killing within neutrophil phagosomes. Collectively, our data show that myeloperoxidase‐derived oxidants react with S. aureus inside neutrophil phagosomes, leading to partial BSH oxidation, and contribute to bacterial killing. However, BSH offers only limited protection against the neutrophil's multifaceted killing mechanisms. |
format | Online Article Text |
id | pubmed-9796752 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-97967522023-01-04 Oxidation of bacillithiol during killing of Staphylococcus aureus USA300 inside neutrophil phagosomes Ashby, Louisa V Springer, Reuben Loi, Vu Van Antelmann, Haike Hampton, Mark B Kettle, Anthony J Dickerhof, Nina J Leukoc Biol Spotlight on Leading Edge Research Targeting immune evasion tactics of pathogenic bacteria may hold the key to treating recalcitrant bacterial infections. Staphylococcus aureus produces bacillithiol (BSH), its major low‐molecular‐weight thiol, which is thought to protect this opportunistic human pathogen against the bombardment of oxidants inside neutrophil phagosomes. Here, we show that BSH was oxidized when human neutrophils phagocytosed S. aureus, but provided limited protection to the bacteria. We used mass spectrometry to measure the oxidation of BSH upon exposure of S. aureus USA300 to either a bolus of hypochlorous acid (HOCl) or a flux generated by the neutrophil enzyme myeloperoxidase. Oxidation of BSH and loss of bacterial viability were strongly correlated (r = 0.99, p < 0.001). BSH was fully oxidized after exposure of S. aureus to lethal doses of HOCl. However, there was no relationship between the initial BSH levels and the dose of HOCl required for bacterial killing. In contrast to the HOCl systems, only 50% of total BSH was oxidized when neutrophils killed the majority of phagocytosed bacteria. Oxidation of BSH was decreased upon inhibition of myeloperoxidase, implicating HOCl in phagosomal BSH oxidation. A BSH‐deficient S. aureus USA300 mutant was slightly more susceptible to treatment with either HOCl or ammonia chloramine, or to killing within neutrophil phagosomes. Collectively, our data show that myeloperoxidase‐derived oxidants react with S. aureus inside neutrophil phagosomes, leading to partial BSH oxidation, and contribute to bacterial killing. However, BSH offers only limited protection against the neutrophil's multifaceted killing mechanisms. John Wiley and Sons Inc. 2022-05-27 2022-10 /pmc/articles/PMC9796752/ /pubmed/35621076 http://dx.doi.org/10.1002/JLB.4HI1021-538RR Text en © 2022 The Authors. Journal of Leukocyte Biology published by Wiley Periodicals LLC on behalf of Society for Leukocyte Biology. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Spotlight on Leading Edge Research Ashby, Louisa V Springer, Reuben Loi, Vu Van Antelmann, Haike Hampton, Mark B Kettle, Anthony J Dickerhof, Nina Oxidation of bacillithiol during killing of Staphylococcus aureus USA300 inside neutrophil phagosomes |
title | Oxidation of bacillithiol during killing of Staphylococcus aureus USA300 inside neutrophil phagosomes |
title_full | Oxidation of bacillithiol during killing of Staphylococcus aureus USA300 inside neutrophil phagosomes |
title_fullStr | Oxidation of bacillithiol during killing of Staphylococcus aureus USA300 inside neutrophil phagosomes |
title_full_unstemmed | Oxidation of bacillithiol during killing of Staphylococcus aureus USA300 inside neutrophil phagosomes |
title_short | Oxidation of bacillithiol during killing of Staphylococcus aureus USA300 inside neutrophil phagosomes |
title_sort | oxidation of bacillithiol during killing of staphylococcus aureus usa300 inside neutrophil phagosomes |
topic | Spotlight on Leading Edge Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9796752/ https://www.ncbi.nlm.nih.gov/pubmed/35621076 http://dx.doi.org/10.1002/JLB.4HI1021-538RR |
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