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Imaging Mycobacterium tuberculosis in Mice with Reporter Enzyme Fluorescence
Published on: February 26, 2018
Accelerated detection of Mycobacterium tuberculosis genes essential for bacterial survival in guinea pigs, compared
Sanjay K Jain1, S Moises Hernandez-Abanto, Qi-Jian Cheng
1Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. sjain5@jhmi.edu
Background:
Mouse and guinea pig models have been used to identify Mycobacterium tuberculosis mutants attenuated for survival. However, unlike mice, M. tuberculosis-infected guinea pigs form caseating granulomas, which may simulate human disease more closely.
Methods:
We used designer arrays for defined mutant analysis, a high-throughput subtractive competition assay, for genotypically defined M. tuberculosis mutants and compared the survival of the same mutant pools in guinea pig and mouse aerosol models. Selected mutants found to be attenuated in either aerosol model were also analyzed in the mouse hollow-fiber model.
Results:
M. tuberculosis mutants representing 74 genes were tested. Eighteen M. tuberculosis mutants were attenuated for survival in either aerosol model, with 70% of selected mutants also attenuated in the mouse hollow-fiber model. The majority of attenuated mutants in the mouse aerosol model were detected only after 90 days of infection. There was a high degree of concordance between the genes identified by the 2 aerosol models, with detection being significantly earlier in the guinea pig (P<.0003).
Conclusions:
We identified M. tuberculosis genes required for survival in mammalian lungs. The majority of mouse late-stage survival mutants were detected significantly earlier in the guinea pig, which suggests that differences in tuberculosis-induced lung pathologic changes may account for this accelerated detection.
Insights
Guinea pigs provide a more sensitive model for identifying Mycobacterium tuberculosis survival genes. Early detection of attenuated mutants in guinea pigs aids in understanding tuberculosis pathogenesis.
Area of Science:
- Microbiology
- Infectious Diseases
- Tuberculosis Research
Background:
- Mouse and guinea pig models are used to study Mycobacterium tuberculosis (M. tuberculosis) survival.
- Guinea pigs exhibit caseating granulomas, mimicking human tuberculosis more closely than mice.
Purpose of the Study:
- To identify M. tuberculosis genes essential for survival in mammalian lungs.
- To compare the efficacy of mouse and guinea pig models in detecting attenuated M. tuberculosis mutants.
Main Methods:
- Utilized designer arrays for defined mutant analysis and high-throughput subtractive competition assays.
- Compared M. tuberculosis mutant pool survival in guinea pig and mouse aerosol models.
- Analyzed selected attenuated mutants in the mouse hollow-fiber model.
Main Results:
- Tested M. tuberculosis mutants for 74 genes; 18 showed attenuated survival in aerosol models.
- 70% of selected attenuated mutants were also identified in the mouse hollow-fiber model.
- Mutant detection was significantly earlier in the guinea pig model (P<.0003) compared to the mouse model.
Conclusions:
- Identified key M. tuberculosis genes required for survival in mammalian lungs.
- The guinea pig model offers accelerated detection of attenuated mutants compared to the mouse model.
- Lung pathology differences likely explain the earlier detection in guinea pigs, enhancing tuberculosis research.
