The absence of murine cathelicidin-related antimicrobial peptide impacts host responses enhancing Salmonella enterica se
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Gut Pathogens Open Access
RESEARCH
The absence of murine cathelicidin‑related antimicrobial peptide impacts host responses enhancing Salmonella enterica serovar Typhimurium infection Danisa M. Bescucci1,2, Sandra T. Clarke1,2, Catherine L. J. Brown1,3, Valerie F. Boras4, Tony Montina5,6, Richard R. E. Uwiera2 and G. Douglas Inglis1*
Abstract 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 m CRAMP+/+ 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. Keywords: Mice, Cathelicidin, mCRAMP, Salmonella enterica Typhimurium, Microbiota, Colonization resistance
*Correspondence: [email protected] 1 Lethbridge Research and Development Centre, Agriculture and AgriFood Canada, Lethbridge, AB, Canada Full list of author information is available at the end of the article
Background Host-defense peptides are an evolutionary conserved component of the innate immune system that play an essential role in protection of the host [1]. Antimicrobial peptides are comprised of defensins, C-type lectins, and cathelicidins [2]. Cathelicidins are peptides
© Her Majesty the Queen in Right of Canada as represented by the Minister of Agriculture and Agri-Food Canada 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, a
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