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  • Title: Streptococcus pneumoniae deficient in pneumolysin or autolysin has reduced virulence in meningitis.
    Author: Hirst RA, Gosai B, Rutman A, Guerin CJ, Nicotera P, Andrew PW, O'Callaghan C.
    Journal: J Infect Dis; 2008 Mar 01; 197(5):744-51. PubMed ID: 18260758.
    Abstract:
    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 (DeltaPly) 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 DeltaPly 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 DeltaPly 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.
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