Dataset Information

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

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 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. Ifn?, Kc, Inos, Il1?, RegIII?). 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.

SUBMITTER: Bescucci DM

PROVIDER: S-EPMC7666523 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Bescucci Danisa M DM Clarke Sandra T ST Brown Catherine L J CLJ Boras Valerie F VF Montina Tony T Uwiera Richard R E RRE Inglis G Douglas GD

Gut pathogens 20201113 1

<h4>Background</h4>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<sup>-/-</sup> and mCRAMP<sup>+/+</sup> mice (± streptomycin) were orally inoculated with S. enterica serovar Typhimuri ...[more]

PMID: 33292444

Similar Datasets

Project description:FinO domain proteins such as ProQ of the model pathogen Salmonella enterica have emerged as a new class of major RNA-binding proteins in bacteria. ProQ has been shown to target hundreds of transcripts, including mRNAs from many virulence regions, but its role, if any, in bacterial pathogenesis has not been studied. Here, using a Dual RNA-seq approach to profile ProQ-dependent gene expression changes as Salmonella infects human cells, we reveal dysregulation of bacterial motility, chemotaxis, and virulence genes which is accompanied by altered MAPK (mitogen-activated protein kinase) signaling in the host. Comparison with the other major RNA chaperone in Salmonella, Hfq, reinforces the notion that these two global RNA-binding proteins work in parallel to ensure full virulence. Of newly discovered infection-associated ProQ-bound small noncoding RNAs (sRNAs), we show that the 3'UTR-derived sRNA STnc540 is capable of repressing an infection-induced magnesium transporter mRNA in a ProQ-dependent manner. Together, this comprehensive study uncovers the relevance of ProQ for Salmonella pathogenesis and highlights the importance of RNA-binding proteins in regulating bacterial virulence programs.IMPORTANCE The protein ProQ has recently been discovered as the centerpiece of a previously overlooked "third domain" of small RNA-mediated control of gene expression in bacteria. As in vitro work continues to reveal molecular mechanisms, it is also important to understand how ProQ affects the life cycle of bacterial pathogens as these pathogens infect eukaryotic cells. Here, we have determined how ProQ shapes Salmonella virulence and how the activities of this RNA-binding protein compare with those of Hfq, another central protein in RNA-based gene regulation in this and other bacteria. To this end, we apply global transcriptomics of pathogen and host cells during infection. In doing so, we reveal ProQ-dependent transcript changes in key virulence and host immune pathways. Moreover, we differentiate the roles of ProQ from those of Hfq during infection, for both coding and noncoding transcripts, and provide an important resource for those interested in ProQ-dependent small RNAs in enteric bacteria.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets