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Updated: May 5, 2026
Humanized Mouse Model to Study Bacterial Infections Targeting the Microvasculature
Published on: April 1, 2014
Developing a Novel Murine Meningococcal Meningitis Model Using a Capsule-Null Bacterial Strain
Viorela-I Caracoti1, Costin-Ș Caracoti1,2, Diana L Ancuța2,3
1Faculty of Medicine, Microbiology Discipline II, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania.
Background:
Neisseria meningitidis (meningococcus) is a Gram-negative bacterium that colonises the nasopharynx of about 10% of the healthy human population. Under certain conditions, it spreads into the body, causing infections with high morbidity and mortality rates. Although the capsule is the key virulence factor, unencapsulated strains have proved to possess significant clinical implications as well. Meningococcal meningitis is a primarily human infection, with limited animal models that are dependent on a variety of parameters such as bacterial virulence and mouse strain. In this study, we aimed to develop a murine Neisseria meningitidis meningitis model to be used in the study of various antimicrobial compounds.
Method:
We used a capsule-deficient Neisseria meningitidis strain that was thoroughly analysed through various methods. The bacterial strain was incubated for 48 h in brain-heart infusion (BHI) broth before being concentrated and injected intracisternally to bypass the blood-brain barrier in CD-1 mice. This prolonged incubation time was a key factor in increasing the virulence of the bacterial strain. A total of three more differently prepared inoculums were tested to further solidify the importance of the protocol (a 24-h incubated inoculum, a diluted inoculum, and an inactivated inoculum). Antibiotic treatment groups were also established. The clinical parameters and number of deaths were recorded over a period of 5 days, and comatose mice with no chance of recovery were euthanised.
Results:
The bacterial strain was confirmed to have no capsule but was found to harbour a total of 56 genes coding virulence factors, and its antibiotic susceptibility was established. Meningitis was confirmed through positive tissue culture and histological evaluation, where specific lesions were observed, such as perivascular sheaths with inflammatory infiltrate. In the treatment groups, survival rates were significantly higher (up to 81.25% in one of the treatment groups compared to 18.75% in the control group).
Conclusion:
We managed to successfully develop a cost-efficient murine (using simple CD-1 mice instead of expensive transgenic mice) meningococcal meningitis model using an unencapsulated strain with a novel method of preparation.
Insights
Researchers developed a cost-effective mouse model for meningococcal meningitis using an unencapsulated Neisseria meningitidis strain. This new model aids in studying antimicrobial compounds against this serious infection.
Area of Science:
- Microbiology
- Infectious Diseases
- Animal Models
Background:
- Neisseria meningitidis colonizes the nasopharynx in 10% of healthy individuals.
- While encapsulated strains are common, unencapsulated strains can also cause severe infections.
- Existing animal models for meningococcal meningitis are limited and complex.
Purpose of the Study:
- To develop a cost-efficient murine model for studying Neisseria meningitidis meningitis.
- To facilitate research on antimicrobial compounds against meningococcal infections.
Main Methods:
- Utilized a capsule-deficient Neisseria meningitidis strain.
- Incubated the bacterial strain for 48 hours to enhance virulence.
- Administered the concentrated bacterial inoculum intracisternally in CD-1 mice.
- Established antibiotic treatment groups and monitored clinical outcomes for 5 days.
Main Results:
- Confirmed meningitis through positive tissue cultures and histological analysis showing characteristic lesions.
- The unencapsulated strain possessed 56 virulence factor genes.
- Antibiotic treatment significantly increased survival rates compared to the control group (up to 81.25% vs. 18.75%).
Conclusions:
- Successfully developed a cost-efficient murine model for meningococcal meningitis.
- The model employs an unencapsulated strain and a novel preparation method.
- This model is suitable for evaluating antimicrobial therapies.
