Streptococcus pneumoniae deficient in pneumolysin or autolysin has reduced virulence in meningitis

Background. The role played by pneumolysin and autolysin in pneumococcal meningitis is poorly understood. Methods. A rat model was used to investigate the disease, in which surgical implantation of a cisternal catheter allowed bacterial instillation and cerebrospinal fluid (CSF) sampling. Results. CSF infection of rats with wild-type pneumococci caused meningitis within 26 h, whereas isogenic mutants that do not express pneumolysin (Delta Ply) or autolysin (LytA(-)) caused very mild or no disease. Wild-type infections resulted in pneumococci in the CSF and cortical homogenates, but a minority of the rats infected with Delta Ply or LytA(-) had bacteria in these locations at 26 h. Leukocyte numbers in the CSF were similar after infection with all pneumococci; however, neutrophils and monocytes predominated after wild-type infection, whereas lymphocytes and atypical lymphocytes predominated after infection with the mutants. Wild-type pneumococci caused disruption to the ependyma, but this was not observed in rats infected with Delta Ply or LytA(-). Cells surrounding the ventricles in wild type-infected animals expressed caspase 3, and astrocytes had hypertrophy; both findings were absent in rats infected with the mutants. Conclusions. This study provides strong in vivo evidence that pneumolysin and autolysin play crucial roles in the pathogenesis of pneumococcal meningitis.