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.
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.
Authors: María Morales; Pedro García; Adela G de la Campa; Josefina Liñares; Carmen Ardanuy; Ernesto García Journal: J Bacteriol Date: 2010-03-19 Impact factor: 3.490
Authors: Elisa Ramos-Sevillano; Ana Urzainqui; Susana Campuzano; Miriam Moscoso; Fernando González-Camacho; Mirian Domenech; Santiago Rodríguez de Córdoba; Francisco Sánchez-Madrid; Jeremy S Brown; Ernesto García; Jose Yuste Journal: Infect Immun Date: 2014-11-17 Impact factor: 3.441
Authors: Jorge E Vidal; Herbert P Ludewick; Rebekah M Kunkel; Dorothea Zähner; Keith P Klugman Journal: Infect Immun Date: 2011-08-08 Impact factor: 3.441