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A mouse model of Staphylococcus aureus small intestinal infection.

ABSTRACT: Introduction. Staphylococcus aureus is a recognised cause of foodborne intoxication and antibiotic-associated diarrhoea (AAD), which are both mediated by staphylococcal enterotoxins. However, unlike foodborne intoxication, AAD appears to require infection of the host. While S. aureus intoxication is widely studied, little is known about S. aureus pathogenesis in the context of gastrointestinal infection.Aim. To develop a mouse model of S. aureus gastrointestinal infection.Methodology. An established AAD mouse model was adapted for S. aureus infection, and damage observed via histopathological analysis and immunostaining of intestinal tissues.Results. Various strains colonised the mouse model, and analysis showed that although clinical signs of disease were not seen, S. aureus infection induced damage in the small intestine, disrupting host structures essential for epithelial integrity. Studies using a staphylococcal enterotoxin B mutant showed that this toxin may contribute to damage during gastrointestinal infection.Conclusion. This work presents a new mouse model of S. aureus gastrointestinal infection, while also providing insight into the pathogenesis of S. aureus in the gut.

SUBMITTER: Larcombe S

PROVIDER: S-EPMC7431102 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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A mouse model of Staphylococcus aureus small intestinal infection.

Larcombe Sarah S Jiang Jhih-Hang JH Hutton Melanie L ML Abud Helen E HE Peleg Anton Y AY Lyras Dena D

Journal of medical microbiology 20200131 2

Introduction. Staphylococcus aureus is a recognised cause of foodborne intoxication and antibiotic-associated diarrhoea (AAD), which are both mediated by staphylococcal enterotoxins. However, unlike foodborne intoxication, AAD appears to require infection of the host. While S. aureus intoxication is widely studied, little is known about S. aureus pathogenesis in the context of gastrointestinal infection.Aim. To develop a mouse model of S. aureus gastroin ...[more]

PMID: 32004137

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Project description:Staphylococcus aureus is a leading cause of skin and soft tissue infections (SSTI), which are primarily self-limiting. We conducted a comprehensive analysis of the host transcriptome during a S. aureus SSTI to provide insight on the protective mechanisms that thwart these infections. We utilized a murine SSTI model in which one ear is epicutaneously challenged while the other is not. We then harvested these infected and uninfected ears, as well as ears from naïve mice, at one, four, and seven days post-challenge, and performed RNA sequencing (RNA-seq) using the Illumina platform. RNA-seq data demonstrated a robust response at the site of infection. Comparison of gene expression profiles between infected ears and the non-infected ears of challenged mice defined the local response to infection, while comparisons of expression profiles of non-infected ears from challenged mice to ears of naïve mice revealed changes in gene expression levels away from the site indicative of a systemic response. Over 1000 genes exhibited increased expression locally at all tested time points. The local response was more robust than the systemic response. Through evaluation of the RNA-seq data using the Upstream Regulator Analytic as part of the Ingenuity Pathway Analysis software package, we found that changes in the activation and inhibition of regulatory pathways happen first locally, and lag behind systemically. The activated pathways are highly similar at all three time points during SSTI, suggesting a stable global response over time. Transcript increases and pathway activation involve pro- and anti-inflammatory mediators, chemotaxis, cell signaling, keratins, and TH1/TH17 cytokines. Transcript decreases and pathway inhibition demonstrate that metabolic genes and anti-inflammatory pathways are repressed. These data provide insight on the host responses that may aid in resolution of this self-limited S. aureus infection, and may shed light on potential immune correlates of protection for staphylococcal SSTI.

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A mouse model of Staphylococcus aureus small intestinal infection.

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A mouse model of <i>Staphylococcus aureus</i> small intestinal infection.

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