Streptococcus pneumoniae deficient in pneumolysin or autolysin has reduced virulence in meningitis. 2008

Robert A Hirst, and Bejal Gosai, and Andrew Rutman, and Christopher J Guerin, and Pierluigi Nicotera, and Peter W Andrew, and Christopher O'Callaghan
Department of Infection, Immunity, and Inflammation, University of Leicester, Leicester, United Kingdom. rah9@le.ac.uk

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.

UI MeSH Term Description Entries
D008297 Male Males
D008586 Meningitis, Pneumococcal An acute purulent infection of the meninges and subarachnoid space caused by Streptococcus pneumoniae, most prevalent in children and adults over the age of 60. This illness may be associated with OTITIS MEDIA; MASTOIDITIS; SINUSITIS; RESPIRATORY TRACT INFECTIONS; sickle cell disease (ANEMIA, SICKLE CELL); skull fractures; and other disorders. Clinical manifestations include FEVER; HEADACHE; neck stiffness; and somnolence followed by SEIZURES; focal neurologic deficits (notably DEAFNESS); and COMA. (From Miller et al., Merritt's Textbook of Neurology, 9th ed, p111) Meningitis, Streptococcus pneumoniae,Experimental Pneumococcal Meningitis,Meningitis, Pneumococcal, Experimental,Meningitis, Pneumococcal, Penicillin-Resistant,Meningitis, Pneumococcal, Recurrent,Experimental Pneumococcal Meningitides,Meningitides, Streptococcus pneumoniae,Meningitis, Experimental Pneumococcal,Pneumococcal Meningitides,Pneumococcal Meningitides, Experimental,Pneumococcal Meningitis,Pneumococcal Meningitis, Experimental,Streptococcus pneumoniae Meningitides,Streptococcus pneumoniae Meningitis
D009238 N-Acetylmuramoyl-L-alanine Amidase An autolytic enzyme bound to the surface of bacterial cell walls. It catalyzes the hydrolysis of the link between N-acetylmuramoyl residues and L-amino acid residues in certain cell wall glycopeptides, particularly peptidoglycan. EC 3.5.1.28. Mucopeptide Amidohydrolase,Autolysin,LE-Enzyme,Murein Hydrolase,Peptidoglycan Hydrolase,T7 Endolysin,T7 Lysozyme,Amidase, N-Acetylmuramoyl-L-alanine,Amidohydrolase, Mucopeptide,Endolysin, T7,Hydrolase, Murein,Hydrolase, Peptidoglycan,LE Enzyme,Lysozyme, T7,N Acetylmuramoyl L alanine Amidase
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D005798 Genes, Bacterial The functional hereditary units of BACTERIA. Bacterial Gene,Bacterial Genes,Gene, Bacterial
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001426 Bacterial Proteins Proteins found in any species of bacterium. Bacterial Gene Products,Bacterial Gene Proteins,Gene Products, Bacterial,Bacterial Gene Product,Bacterial Gene Protein,Bacterial Protein,Gene Product, Bacterial,Gene Protein, Bacterial,Gene Proteins, Bacterial,Protein, Bacterial,Proteins, Bacterial
D013296 Streptococcus pneumoniae A gram-positive organism found in the upper respiratory tract, inflammatory exudates, and various body fluids of normal and/or diseased humans and, rarely, domestic animals. Diplococcus pneumoniae,Pneumococcus
D013301 Streptolysins Exotoxins produced by certain strains of streptococci, particularly those of group A (STREPTOCOCCUS PYOGENES), that cause HEMOLYSIS. Streptolysin
D014774 Virulence The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. The pathogenic capacity of an organism is determined by its VIRULENCE FACTORS. Pathogenicity

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