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The absence of murine cathelicidin-related antimicrobial peptide impacts host responses enhancing Salmonella enterica serovar Typhimurium infection

BACKGROUND: Cathelicidins are a class of antimicrobial peptide, and the murine cathelicidin-related antimicrobial peptide (mCRAMP) has been demonstrated in vitro to impair Salmonella enterica serovar Typhimurium proliferation. However, the impact of mCRAMP on host responses and the microbiota follow...

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Autores principales: Bescucci, Danisa M., Clarke, Sandra T., Brown, Catherine L. J., Boras, Valerie F., Montina, Tony, Uwiera, Richard R. E., Inglis, G. Douglas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666523/
https://www.ncbi.nlm.nih.gov/pubmed/33292444
http://dx.doi.org/10.1186/s13099-020-00386-1
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author Bescucci, Danisa M.
Clarke, Sandra T.
Brown, Catherine L. J.
Boras, Valerie F.
Montina, Tony
Uwiera, Richard R. E.
Inglis, G. Douglas
author_facet Bescucci, Danisa M.
Clarke, Sandra T.
Brown, Catherine L. J.
Boras, Valerie F.
Montina, Tony
Uwiera, Richard R. E.
Inglis, G. Douglas
author_sort Bescucci, Danisa M.
collection PubMed
description BACKGROUND: Cathelicidins are a class of antimicrobial peptide, and the murine cathelicidin-related antimicrobial peptide (mCRAMP) has been demonstrated in vitro to impair Salmonella enterica serovar Typhimurium proliferation. However, the impact of mCRAMP on host responses and the microbiota following S. Typhimurium infection has not been determined. In this study mCRAMP(−/−) and mCRAMP(+/+) mice (± streptomycin) were orally inoculated with S. enterica serovar Typhimurium DT104 (SA +), and impacts on the host and enteric bacterial communities were temporally evaluated. RESULTS: Higher densities of the pathogen were observed in cecal digesta and associated with mucosa in SA+/mCRAMP(−/−) mice that were pretreated (ST+) and not pretreated (ST−) with streptomycin at 24 h post-inoculation (hpi). Both SA+/ST+/mCRAMP(−/−) and SA+/ST−/mCRAMP(−/−) mice were more susceptible to infection exhibiting greater histopathologic changes (e.g. epithelial injury, leukocyte infiltration, goblet cell loss) at 48 hpi. Correspondingly, immune responses in SA+/ST+/mCRAMP(–/−) and SA+/ST−/mCRAMP(–/−) mice were affected (e.g. Ifnγ, Kc, Inos, Il1β, RegIIIγ). Systemic dissemination of the pathogen was characterized by metabolomics, and the liver metabolome was affected to a greater degree in SA+/ST+/mCRAMP(–/−) and SA+/ST−/mCRAMP(–/−) mice (e.g. taurine, cadaverine). Treatment-specific changes to the structure of the enteric microbiota were associated with infection and mCRAMP deficiency, with a higher abundance of Enterobacteriaceae and Veillonellaceae observed in infected null mice. The microbiota of mice that were administered the antibiotic and infected with Salmonella was dominated by Proteobacteria. CONCLUSION: The study findings showed that the absence of mCRAMP modulated both host responses and the enteric microbiota enhancing local and systemic infection by Salmonella Typhimurium.
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spelling pubmed-76665232020-11-16 The absence of murine cathelicidin-related antimicrobial peptide impacts host responses enhancing Salmonella enterica serovar Typhimurium infection Bescucci, Danisa M. Clarke, Sandra T. Brown, Catherine L. J. Boras, Valerie F. Montina, Tony Uwiera, Richard R. E. Inglis, G. Douglas Gut Pathog Research BACKGROUND: Cathelicidins are a class of antimicrobial peptide, and the murine cathelicidin-related antimicrobial peptide (mCRAMP) has been demonstrated in vitro to impair Salmonella enterica serovar Typhimurium proliferation. However, the impact of mCRAMP on host responses and the microbiota following S. Typhimurium infection has not been determined. In this study mCRAMP(−/−) and mCRAMP(+/+) mice (± streptomycin) were orally inoculated with S. enterica serovar Typhimurium DT104 (SA +), and impacts on the host and enteric bacterial communities were temporally evaluated. RESULTS: Higher densities of the pathogen were observed in cecal digesta and associated with mucosa in SA+/mCRAMP(−/−) mice that were pretreated (ST+) and not pretreated (ST−) with streptomycin at 24 h post-inoculation (hpi). Both SA+/ST+/mCRAMP(−/−) and SA+/ST−/mCRAMP(−/−) mice were more susceptible to infection exhibiting greater histopathologic changes (e.g. epithelial injury, leukocyte infiltration, goblet cell loss) at 48 hpi. Correspondingly, immune responses in SA+/ST+/mCRAMP(–/−) and SA+/ST−/mCRAMP(–/−) mice were affected (e.g. Ifnγ, Kc, Inos, Il1β, RegIIIγ). Systemic dissemination of the pathogen was characterized by metabolomics, and the liver metabolome was affected to a greater degree in SA+/ST+/mCRAMP(–/−) and SA+/ST−/mCRAMP(–/−) mice (e.g. taurine, cadaverine). Treatment-specific changes to the structure of the enteric microbiota were associated with infection and mCRAMP deficiency, with a higher abundance of Enterobacteriaceae and Veillonellaceae observed in infected null mice. The microbiota of mice that were administered the antibiotic and infected with Salmonella was dominated by Proteobacteria. CONCLUSION: The study findings showed that the absence of mCRAMP modulated both host responses and the enteric microbiota enhancing local and systemic infection by Salmonella Typhimurium. BioMed Central 2020-11-13 /pmc/articles/PMC7666523/ /pubmed/33292444 http://dx.doi.org/10.1186/s13099-020-00386-1 Text en © Her Majesty the Queen in Right of Canada as represented by the Minister of Agriculture and Agri-Food 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Bescucci, Danisa M.
Clarke, Sandra T.
Brown, Catherine L. J.
Boras, Valerie F.
Montina, Tony
Uwiera, Richard R. E.
Inglis, G. Douglas
The absence of murine cathelicidin-related antimicrobial peptide impacts host responses enhancing Salmonella enterica serovar Typhimurium infection
title The absence of murine cathelicidin-related antimicrobial peptide impacts host responses enhancing Salmonella enterica serovar Typhimurium infection
title_full The absence of murine cathelicidin-related antimicrobial peptide impacts host responses enhancing Salmonella enterica serovar Typhimurium infection
title_fullStr The absence of murine cathelicidin-related antimicrobial peptide impacts host responses enhancing Salmonella enterica serovar Typhimurium infection
title_full_unstemmed The absence of murine cathelicidin-related antimicrobial peptide impacts host responses enhancing Salmonella enterica serovar Typhimurium infection
title_short The absence of murine cathelicidin-related antimicrobial peptide impacts host responses enhancing Salmonella enterica serovar Typhimurium infection
title_sort absence of murine cathelicidin-related antimicrobial peptide impacts host responses enhancing salmonella enterica serovar typhimurium infection
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666523/
https://www.ncbi.nlm.nih.gov/pubmed/33292444
http://dx.doi.org/10.1186/s13099-020-00386-1
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