A defined microbiota mouse model for Salmonella Paratyphi A oral infection

Caleb Skow1,2, Logan C Ott1,2, Michael J Wannemuehler1,3

  • 1Interdepartmental Graduate Microbiology Program, Iowa State University, Ames, IA, United States.

Abstract

Insights

This study introduces a new mouse model using altered Schaedler flora (ASF) mice to study Salmonella Paratyphi A (SPtA) infection. The model effectively replicates human enteric fever symptoms, aiding research into this emerging pathogen.

Area of Science:

  • Microbiology
  • Immunology
  • Pathogenesis Research

Background:

  • Salmonella Paratyphi A (SPtA) is an emerging human pathogen causing enteric fever.
  • Limited research exists due to the lack of suitable animal models for SPtA infection.

Purpose of the Study:

  • To develop and validate a cost-effective animal model for studying SPtA pathogenesis.
  • To investigate SPtA colonization, persistence, and host responses in a murine model.

Main Methods:

  • Utilized gnotobiotic mice with altered Schaedler flora (ASF) on different genetic backgrounds.
  • Challenged mice with SPtA orally and assessed pathogen colonization in tissues.
  • Analyzed gut microbiota, cytokine expression, tight junction proteins, and histopathology.

Main Results:

  • ASF mouse model demonstrated that inflammatory state and sex influenced SPtA colonization.
  • 129S6/SvEv IL10-/- ASF mice infected with SPtA showed extraintestinal dissemination, cytokine inhibition, and progressive pathology, mirroring human disease.
  • The ASF model allowed for studying SPtA in a defined microbiome without antibiotic treatment limitations.

Conclusions:

  • ASF mice provide a suitable, low-cost model for SPtA infection research.
  • The IL10-/- ASF mouse model facilitates the study of SPtA extraintestinal invasion and disease progression.
  • This model aids in understanding SPtA pathogenesis and microbiome interactions.

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