A defined microbiota mouse model for Salmonella Paratyphi A oral infection

Salmonella Paratyphi A (SPtA) is an emerging pathogen that primarily infects humans and causes enteric fever, yet it has not received sufficient research attention. To facilitate further investigation, an appropriate animal model is necessary for testing SPtA infection.

In this study, we utilized gnotobiotic mice harboring the altered Schaedler flora (ASF) from either C3H/HeN or 129S6/SvEv genetic backgrounds. These mice, subjected to various inflammatory conditions, were orally challenged with SPtA. The colonization and persistence of the pathogen were assessed in both intestinal and extraintestinal tissues, while also examining changes in gut microbiota, the expression of tight junction proteins, cytokines, and histopathological changes.

Our findings revealed that both the inflammatory state and the sex of the ASF mice significantly affected the colonization of SPtA. Notably, infection of the 129S6/SvEv IL10^-/- mice with SPtA replicated key features observed in humans. This included the extraintestinal dissemination of SPtA, the inhibition of pro-inflammatory cytokines, and progressively worsening pathological changes over time following infection in IL10^-/- ASF mice.

The results of this study suggest that ASF mice represent a suitable low-cost model for investigating the pathogenesis of SPtA infection. The presence of ASF creates an open niche for SPtA colonization, allowing for the retention of a defined microbiome. This enables researchers to study perturbations in the microbiome without the limitations inherent to an antibiotic-treated model alternative. Furthermore, the chronic inflammatory conditions associated with IL10^-/- phenotype enable SPtA extraintestinal invasion and disease progress in the murine host, facilitating a functional model of SPtA pathogenesis.