Contribution of different pneumococcal virulence factors to experimental meningitis in mice

Pneumococcal meningitis (PM) is a life-threatening disease with a high case-fatality rate and elevated risk for serious neurological sequelae. In this study, we investigated the contribution of three major virulence factors of Streptococcus pneumoniae, the capsule, pneumococcal surface protein A (Ps...

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Bibliographic Details
Published in:BMC infectious diseases 2013-09, Vol.13 (1), p.444-444, Article 444
Main Authors: Ricci, Susanna, Gerlini, Alice, Pammolli, Andrea, Chiavolini, Damiana, Braione, Velia, Tripodi, Sergio Antonio, Colombari, Bruna, Blasi, Elisabetta, Oggioni, Marco Rinaldo, Peppoloni, Samuele, Pozzi, Gianni
Format: Article
Language:English
Subjects:
Analysis
Animal experimentation
Animals
Bacterial Capsules - genetics
Bacterial Capsules - metabolism
Bacterial Proteins - genetics
Bacterial Proteins - metabolism
Brain damage
Development and progression
Disease Models, Animal
Female
Humans
Meningitis
Meningitis, Pneumococcal - microbiology
Meningitis, Pneumococcal - mortality
Mice
Microbiology
Neurons
Physiological aspects
Streptococcus pneumoniae
Streptococcus pneumoniae - genetics
Streptococcus pneumoniae - metabolism
Streptococcus pneumoniae - pathogenicity
Studies
Vaccines
Virulence (Microbiology)
Virulence Factors - genetics
Virulence Factors - metabolism
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Summary:Pneumococcal meningitis (PM) is a life-threatening disease with a high case-fatality rate and elevated risk for serious neurological sequelae. In this study, we investigated the contribution of three major virulence factors of Streptococcus pneumoniae, the capsule, pneumococcal surface protein A (PspA) and C (PspC), to the pathogenesis of experimental PM. Mice were challenged by the intracranial route with the serotype 4 TIGR4 strain (wt) and three isogenic mutants devoid of PspA, PspC, and the capsule. Survival, bacterial counts, and brain histology were carried out. To study the interaction between S. pneumoniae mutants and microglia, phagocytosis and survival experiments were performed using the BV2 mouse microglial cell line. Virulence of the PspC mutant was comparable to that of TIGR4. In contrast, survival of animals challenged with the PspA mutant was significantly increased compared with the wt, and the mutant was also impaired at replicating in the brain and blood of infected mice. Brain histology indicated that all strains, except for the unencapsulated mutant, caused PM. Analysis of inflammation and damage in the brain of mice infected with TIGR4 or its unencapsulated mutant demonstrated that the rough strain was unable to induce inflammation and neuronal injury, even at high challenge doses. Results with BV2 cells showed no differences in phagocytic uptake between wt and mutants. In survival assays, however, the PspA mutant showed significantly reduced survival in microglia compared with the wt. PspA contributed to PM pathogenesis possibly by interacting with microglia at early infection stages, while PspC had limited importance in the disease. The rough mutant did not cause brain inflammation, neuronal damage or mouse death, strengthening the key role of the capsule in PM.
ISSN:1471-2334
1471-2334
DOI:10.1186/1471-2334-13-444