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Updated: Mar 9, 2026
Use of the Invertebrate Galleria mellonella as an Infection Model to Study the Mycobacterium tuberculosis Complex
Published on: June 30, 2019
Murine model of TB meningitis
Umesh Datta Gupta1, Ali Abbas2, Raj Pal Singh Kashyap2
1National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Agra 282004, India.
Background:
Central nervous system (CNS) infections caused by Mycobacterium tuberculosis (MTB) are the most severe forms of extrapulmonary TB (EPTB) due to high levels of mortality and neurological morbidity. Limited studies are available on CNS-TB animal-model development, despite the steady rise in cerebral-TB cases in India over the past decade. This study describes the development of a murine model of CNS-TB using a clinical strain (C3) isolated from the cerebrospinal fluid (CSF) of CNS-TB patients.
Methods:
Groups of mice were infected intravenously with an MTB C3 strain isolated from the CSF of CNS-TB patients in order to mimic the dynamics of actual infection. Brain and lung tissue were evaluated for bacterial burden, as well as histopathology and surrogate markers of TB infection at 30- and 50-days post-infection.
Results:
Mice infected intravenously with MTB C3 strains showed progressive development of CNS disease, with high bacillary burden in the lungs during the initial stage (30days), which eventually disseminated to the brain at a later stage (50days). All C3-infected mice showed elevated levels of mycobacterial antigens and antibodies, as well as increased T cell adenosine deaminase activity in brain homogenates, which explicitly correlated with mycobacterial load in the brain and chronic brain pathology. High mortality rates (60%) were associated with mice infected with the C3 strain as compared to those of controls.
Conclusion:
Our findings demonstrated the design of a novel murine model of CNS-TB using a C3 strain and that replicated events of EPTB dissemination. This model will promote efforts to understand the pathogenesis CNS-TB infection for development of improved therapeutic interventions in the future.
Insights
A new mouse model using a Mycobacterium tuberculosis (MTB) C3 strain effectively replicates central nervous system (CNS) tuberculosis (TB) infection, showing disease progression and high mortality. This model aids in understanding CNS-TB pathogenesis and developing new treatments.
Area of Science:
- Infectious Diseases
- Neurology
- Animal Models
Background:
- Central nervous system (CNS) infections from Mycobacterium tuberculosis (MTB) are severe forms of extrapulmonary TB (EPTB), leading to high mortality and neurological issues.
- Cerebral-TB cases are increasing, yet animal models for CNS-TB are limited.
- This study developed a murine model using a clinical MTB strain (C3) from cerebrospinal fluid (CSF) of CNS-TB patients.
Purpose of the Study:
- To develop and characterize a novel murine model for central nervous system tuberculosis (CNS-TB).
- To mimic the dissemination dynamics of MTB infection from the bloodstream to the brain.
- To provide a platform for studying CNS-TB pathogenesis and evaluating therapeutic interventions.
Main Methods:
- Mice were intravenously infected with a clinical MTB C3 strain, isolated from patient CSF.
- Bacterial burden, histopathology, and surrogate TB markers were assessed in brain and lung tissues at 30 and 50 days post-infection.
Main Results:
- Intravenous MTB C3 infection led to progressive CNS disease, with initial lung bacterial load followed by brain dissemination.
- Infected mice exhibited elevated mycobacterial antigens, antibodies, and T cell adenosine deaminase activity in the brain.
- A high mortality rate (60%) was observed in mice infected with the C3 strain.
Conclusions:
- A novel murine model for CNS-TB was successfully developed using the MTB C3 strain.
- The model replicates key events of extrapulmonary TB dissemination to the CNS.
- This model is crucial for advancing the understanding of CNS-TB pathogenesis and developing effective treatments.
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