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Anti-tuberculosis drug therapy in mice of different inbred strains
Boris V Nikonenko1, Leo Einck, Carol A Nacy
1Sequella, Inc., Rockville, MD 20850, United States. borisnikonenko@sequella.com
Abstract:
Standard anti-tuberculosis (TB) drug therapy had distinct effects on the bacilli burden in mice of DBA/2, C3H, SWR/J, and C57BL/6 inbred strains. To standardize the TB infection process, susceptible DBA/2 mice were infected with 1/10 of the dose used for relatively resistant C57BL/6 mice, such that the lung CFUs were roughly identical 3 weeks after infection when therapy was initiated. We found that TB treatment was more effective in the susceptible DBA/2 mice than in the relatively resistant C57BL/6 mice.
Insights
Standard tuberculosis (TB) drug therapy showed different effects across mouse strains. Treatment was more effective in susceptible DBA/2 mice compared to resistant C57BL/6 mice, despite similar initial infection levels.
Area of Science:
- Immunology
- Microbiology
- Genetics
Background:
- Tuberculosis (TB) is a significant global health challenge.
- Host genetic background influences TB susceptibility and treatment outcomes.
- Understanding strain-specific responses to anti-TB therapy is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the impact of host inbred mouse strain on the efficacy of standard anti-tuberculosis drug therapy.
- To compare the effectiveness of TB treatment in genetically susceptible versus resistant mouse models.
Main Methods:
- Utilized four inbred mouse strains (DBA/2, C3H, SWR/J, C57BL/6) for TB infection studies.
- Standardized the infection process by adjusting initial bacterial dose based on strain susceptibility.
- Initiated standard anti-TB drug therapy when lung colony-forming units (CFUs) were comparable across strains.
Main Results:
- Standard anti-TB drug therapy exhibited distinct effects on bacilli burden across different mouse strains.
- Treatment efficacy varied between susceptible DBA/2 mice and relatively resistant C57BL/6 mice.
- TB treatment was found to be more effective in the susceptible DBA/2 mouse strain.
Conclusions:
- Host genetic factors significantly modulate the response to anti-tuberculosis drug therapy.
- Susceptible mouse strains may show better outcomes with standard TB treatment compared to resistant strains.
- These findings highlight the importance of host genetics in TB treatment strategies.
