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The capsule of Bacillus anthracis protects it from the bactericidal activity of human defensins and other cationic antimicrobial peptides

During infection, Bacillus anthracis bacilli encounter potent antimicrobial peptides (AMPs) such as defensins. We examined the role that B. anthracis capsule plays in protecting bacilli from defensins and other cationic AMPs by comparing their effects on a fully virulent encapsulated wild type (WT)...

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Autores principales: O’Brien, David K., Ribot, Wilson J., Chabot, Donald J., Scorpio, Angelo, Tobery, Steven A., Jelacic, Tanya M., Wu, Zhibin, Friedlander, Arthur M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9560598/
https://www.ncbi.nlm.nih.gov/pubmed/36174087
http://dx.doi.org/10.1371/journal.ppat.1010851
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author O’Brien, David K.
Ribot, Wilson J.
Chabot, Donald J.
Scorpio, Angelo
Tobery, Steven A.
Jelacic, Tanya M.
Wu, Zhibin
Friedlander, Arthur M.
author_facet O’Brien, David K.
Ribot, Wilson J.
Chabot, Donald J.
Scorpio, Angelo
Tobery, Steven A.
Jelacic, Tanya M.
Wu, Zhibin
Friedlander, Arthur M.
author_sort O’Brien, David K.
collection PubMed
description During infection, Bacillus anthracis bacilli encounter potent antimicrobial peptides (AMPs) such as defensins. We examined the role that B. anthracis capsule plays in protecting bacilli from defensins and other cationic AMPs by comparing their effects on a fully virulent encapsulated wild type (WT) strain and an isogenic capsule-deficient capA mutant strain. We identified several human defensins and non-human AMPs that were capable of killing B. anthracis. The human alpha defensins 1–6 (HNP-1-4, HD-5-6), the human beta defensins 1–4 (HBD-1-4), and the non-human AMPs, protegrin, gramicidin D, polymyxin B, nisin, and melittin were all capable of killing both encapsulated WT and non-encapsulated capA mutant B. anthracis. However, non-encapsulated capA mutant bacilli were significantly more susceptible than encapsulated WT bacilli to killing by nearly all of the AMPs tested. We demonstrated that purified capsule bound HBD-2, HBD-3, and HNP-1 in an electrophoretic mobility shift assay. Furthermore, we determined that the capsule layer enveloping WT bacilli bound and trapped HBD-3, substantially reducing the amount reaching the cell wall. To assess whether released capsule might also play a protective role, we pre-incubated HBD-2, HBD-3, or HNP-1 with purified capsule before their addition to non-encapsulated capA mutant bacilli. We found that free capsule completely rescued the capA mutant bacilli from killing by HBD-2 and -3 while killing by HNP-1 was reduced to the level observed with WT bacilli. Together, these results suggest an immune evasion mechanism by which the capsule, both that enveloping the bacilli and released fragments, contributes to virulence by binding to and inhibiting the antimicrobial activity of cationic AMPs.
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spelling pubmed-95605982022-10-14 The capsule of Bacillus anthracis protects it from the bactericidal activity of human defensins and other cationic antimicrobial peptides O’Brien, David K. Ribot, Wilson J. Chabot, Donald J. Scorpio, Angelo Tobery, Steven A. Jelacic, Tanya M. Wu, Zhibin Friedlander, Arthur M. PLoS Pathog Research Article During infection, Bacillus anthracis bacilli encounter potent antimicrobial peptides (AMPs) such as defensins. We examined the role that B. anthracis capsule plays in protecting bacilli from defensins and other cationic AMPs by comparing their effects on a fully virulent encapsulated wild type (WT) strain and an isogenic capsule-deficient capA mutant strain. We identified several human defensins and non-human AMPs that were capable of killing B. anthracis. The human alpha defensins 1–6 (HNP-1-4, HD-5-6), the human beta defensins 1–4 (HBD-1-4), and the non-human AMPs, protegrin, gramicidin D, polymyxin B, nisin, and melittin were all capable of killing both encapsulated WT and non-encapsulated capA mutant B. anthracis. However, non-encapsulated capA mutant bacilli were significantly more susceptible than encapsulated WT bacilli to killing by nearly all of the AMPs tested. We demonstrated that purified capsule bound HBD-2, HBD-3, and HNP-1 in an electrophoretic mobility shift assay. Furthermore, we determined that the capsule layer enveloping WT bacilli bound and trapped HBD-3, substantially reducing the amount reaching the cell wall. To assess whether released capsule might also play a protective role, we pre-incubated HBD-2, HBD-3, or HNP-1 with purified capsule before their addition to non-encapsulated capA mutant bacilli. We found that free capsule completely rescued the capA mutant bacilli from killing by HBD-2 and -3 while killing by HNP-1 was reduced to the level observed with WT bacilli. Together, these results suggest an immune evasion mechanism by which the capsule, both that enveloping the bacilli and released fragments, contributes to virulence by binding to and inhibiting the antimicrobial activity of cationic AMPs. Public Library of Science 2022-09-29 /pmc/articles/PMC9560598/ /pubmed/36174087 http://dx.doi.org/10.1371/journal.ppat.1010851 Text en https://creativecommons.org/publicdomain/zero/1.0/This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication.
spellingShingle Research Article
O’Brien, David K.
Ribot, Wilson J.
Chabot, Donald J.
Scorpio, Angelo
Tobery, Steven A.
Jelacic, Tanya M.
Wu, Zhibin
Friedlander, Arthur M.
The capsule of Bacillus anthracis protects it from the bactericidal activity of human defensins and other cationic antimicrobial peptides
title The capsule of Bacillus anthracis protects it from the bactericidal activity of human defensins and other cationic antimicrobial peptides
title_full The capsule of Bacillus anthracis protects it from the bactericidal activity of human defensins and other cationic antimicrobial peptides
title_fullStr The capsule of Bacillus anthracis protects it from the bactericidal activity of human defensins and other cationic antimicrobial peptides
title_full_unstemmed The capsule of Bacillus anthracis protects it from the bactericidal activity of human defensins and other cationic antimicrobial peptides
title_short The capsule of Bacillus anthracis protects it from the bactericidal activity of human defensins and other cationic antimicrobial peptides
title_sort capsule of bacillus anthracis protects it from the bactericidal activity of human defensins and other cationic antimicrobial peptides
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9560598/
https://www.ncbi.nlm.nih.gov/pubmed/36174087
http://dx.doi.org/10.1371/journal.ppat.1010851
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