Method for inducing experimental pneumococcal meningitis in outbred mice
- Equal contributors
1 Dipartimento di Biologia Molecolare, Laboratorio di Microbiologia Molecolare e Biotecnologia (LA.M.M.B.), Policlinico "Le Scotte" (5° lotto), Università di Siena, Viale Bracci, 53100 Siena, Italy
2 Current address: Evans Medical Research Center, 650 Albany Street, Boston University School of Medicine, Boston Medical Center, Boston, MA 02118, USA
3 Istituto di Anatomia Patologica e Istologia, Policlinico "Le Scotte", Università di Siena, Viale Bracci, 53100 Siena, Italy
4 Dipartimento di Scienze Igienistiche, Microbiologiche e Biostatistiche, Università di Modena e Reggio Emilia, Modena, Via Campi 287, 41100 Modena, Italy
BMC Microbiology 2004, 4:36 doi:10.1186/1471-2180-4-36Published: 22 September 2004
Streptococcus pneumoniae is the leading cause of bacterial meningitis. Pneumococcal meningitis is associated with the highest mortality among bacterial meningitis and it may also lead to neurological sequelae despite the use of antibiotic therapy. Experimental animal models of pneumococcal meningitis are important to study the pathogenesis of meningitis, the host immune response induced after infection, and the efficacy of novel drugs and vaccines.
In the present work, we describe in detail a simple, reproducible and efficient method to induce pneumococcal meningitis in outbred mice by using the intracranial subarachnoidal route of infection. Bacteria were injected into the subarachnoid space through a soft point located 3.5 mm rostral from the bregma. The model was tested with several doses of pneumococci of three capsular serotypes (2, 3 and 4), and mice survival was recorded. Lethal doses killing 50 % of animals infected with type 2, 3 and 4 S. pneumoniae were 3.2 × 10, 2.9 × 10 and 1.9 × 102 colony forming units, respectively. Characterisation of the disease caused by the type 4 strain showed that in moribund mice systemic dissemination of pneumococci to blood and spleen occurred. Histological analysis of the brain of animals infected with type 4 S. pneumoniae proved the induction of meningitis closely resembling the disease in humans.
The proposed method for inducing pneumococcal meningitis in outbred mice is easy-to-perform, fast, cost-effective, and reproducible, irrespective of the serotype of pneumococci used.