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Updated: Jul 15, 2025
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Published on: July 3, 2025
Establishment of persistent enteric mycobacterial infection following streptomycin pre-treatment
Shannon C Duffy1,2,3, Andréanne Lupien1,2,3,4, Youssef Elhaji5
1Department of Microbiology and Immunology, McGill University, Montreal, QC, Canada.
Abstract:
Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of paratuberculosis, a chronic gastrointestinal disease affecting ruminants. This disease remains widespread in part due to the limitations of available diagnostics and vaccines. A representative small animal model of disease could act as a valuable tool for studying its pathogenesis and to develop new methods for paratuberculosis control, but current models are lacking. Streptomycin pre-treatment can reduce colonization resistance and has previously been shown to improve enteric infection in a Salmonella model. Here, we investigated whether streptomycin pre-treatment of mice followed by MAP gavage could act as a model of paratuberculosis which mimics the natural route of infection and disease development in ruminants. The infection outcomes of MAP were compared to M. avium subsp. hominissuis (MAH), an environmental mycobacterium, and M. bovis and M. orygis, two tuberculous mycobacteria. Streptomycin pre-treatment was shown to consistently improve bacterial infection post-oral inoculation. This model led to chronic MAP infection of the intestines and mesenteric lymph nodes (MLNs) up to 24-weeks post-gavage, however there was no evidence of inflammation or disease. These infection outcomes were found to be specific to MAP. When the model was applied to a bacterium of lesser virulence MAH, the infection was comparatively transient. Mice infected with bacteria of greater virulence, M. bovis or M. orygis, developed chronic intestinal and MLN infection with pulmonary disease similar to zoonotic TB. Our findings suggest that a streptomycin pre-treatment mouse model could be applied to future studies to improve enteric infection with MAP and to investigate other modifications underlying MAP enteritis.
Insights
A new mouse model using streptomycin pre-treatment effectively models chronic Mycobacterium avium subsp. paratuberculosis (MAP) infection in the intestines and lymph nodes, aiding paratuberculosis research.
Area of Science:
- Veterinary Microbiology
- Infectious Diseases
- Animal Models
Background:
- Mycobacterium avium subsp. paratuberculosis (MAP) causes paratuberculosis, a significant ruminant disease with limited diagnostics and vaccines.
- Developing a small animal model is crucial for understanding MAP pathogenesis and control strategies.
- Current animal models for paratuberculosis are insufficient.
Purpose of the Study:
- To establish and validate a streptomycin pre-treatment mouse model for paratuberculosis that mimics natural infection routes.
- To compare MAP infection outcomes with other mycobacterial species (MAH, M. bovis, M. orygis) in this model.
- To assess the model's utility for studying MAP enteritis.
Main Methods:
- Mice were pre-treated with streptomycin to reduce colonization resistance.
- Oral gavage with MAP was administered to assess infection establishment and progression.
- Infection outcomes were compared across different mycobacterial species (MAP, MAH, M. bovis, M. orygis).
- Histopathological analysis and bacterial load quantification were performed.
Main Results:
- Streptomycin pre-treatment consistently enhanced bacterial infection following oral inoculation.
- A chronic MAP infection model was established, showing persistent colonization in intestines and mesenteric lymph nodes (MLNs) for up to 24 weeks without overt disease.
- Infection specificity was observed: MAH infection was transient, while M. bovis and M. orygis caused severe disease, including pulmonary manifestations.
- The model demonstrated specificity for MAP, with no signs of inflammation or disease in MAP-infected mice.
Conclusions:
- The streptomycin pre-treatment mouse model provides a valuable tool for studying chronic enteric MAP infections.
- This model can be used to investigate MAP pathogenesis and evaluate novel control measures.
- The model's ability to differentiate infection outcomes based on bacterial virulence is highlighted.
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