Establishment of persistent enteric mycobacterial infection following streptomycin pre-treatment
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...
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| Format: | Article |
| Language: | English |
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BMC
2023-10-01
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| Series: | Gut Pathogens |
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| Online Access: | https://doi.org/10.1186/s13099-023-00573-w |
| _version_ | 1797559439529607168 |
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| author | Shannon C. Duffy Andréanne Lupien Youssef Elhaji Mina Farag Victoria Marcus Marcel A. Behr |
| author_facet | Shannon C. Duffy Andréanne Lupien Youssef Elhaji Mina Farag Victoria Marcus Marcel A. Behr |
| author_sort | Shannon C. Duffy |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T17:45:28Z |
| format | Article |
| id | doaj.art-f5fe20c31fd7432899d2b981fda5ea3a |
| institution | Directory Open Access Journal |
| issn | 1757-4749 |
| language | English |
| last_indexed | 2024-03-10T17:45:28Z |
| publishDate | 2023-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Gut Pathogens |
| spelling | doaj.art-f5fe20c31fd7432899d2b981fda5ea3a2023-11-20T09:33:06ZengBMCGut Pathogens1757-47492023-10-0115111310.1186/s13099-023-00573-wEstablishment of persistent enteric mycobacterial infection following streptomycin pre-treatmentShannon C. Duffy0Andréanne Lupien1Youssef Elhaji2Mina Farag3Victoria Marcus4Marcel A. Behr5Department of Microbiology and Immunology, McGill UniversityDepartment of Microbiology and Immunology, McGill UniversityDiagnostic Genomic Division, Department of Laboratory Medicine and Pathology, Hamad Medical CorporationDepartment of Pathology, McGill UniversityDepartment of Pathology, McGill UniversityDepartment of Microbiology and Immunology, McGill UniversityAbstract 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.https://doi.org/10.1186/s13099-023-00573-wMycobacterium avium subsp. paratuberculosisParatuberculosisCrohn’s diseaseMouse modelsMycobacterium avium subsp. hominissuisMycobacterium bovis |
| spellingShingle | Shannon C. Duffy Andréanne Lupien Youssef Elhaji Mina Farag Victoria Marcus Marcel A. Behr Establishment of persistent enteric mycobacterial infection following streptomycin pre-treatment Gut Pathogens Mycobacterium avium subsp. paratuberculosis Paratuberculosis Crohn’s disease Mouse models Mycobacterium avium subsp. hominissuis Mycobacterium bovis |
| title | Establishment of persistent enteric mycobacterial infection following streptomycin pre-treatment |
| title_full | Establishment of persistent enteric mycobacterial infection following streptomycin pre-treatment |
| title_fullStr | Establishment of persistent enteric mycobacterial infection following streptomycin pre-treatment |
| title_full_unstemmed | Establishment of persistent enteric mycobacterial infection following streptomycin pre-treatment |
| title_short | Establishment of persistent enteric mycobacterial infection following streptomycin pre-treatment |
| title_sort | establishment of persistent enteric mycobacterial infection following streptomycin pre treatment |
| topic | Mycobacterium avium subsp. paratuberculosis Paratuberculosis Crohn’s disease Mouse models Mycobacterium avium subsp. hominissuis Mycobacterium bovis |
| url | https://doi.org/10.1186/s13099-023-00573-w |
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