Bacterial pore-forming cytolysins induce neuronal damage in a rat model of neonatal meningitis

Anja Reiß, Johann S. Braun, Katja Jäger, Dorette Freyer, Gregor Laube, Christoph Bührer, Ursula Felderhoff-Müser, Christine Stadelmann, Victor Nizet, Joerg R. Weber

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)

Abstract

Background. Group B Streptococcus (GBS) and Streptococcus pneumoniae (SP) are leading causes of bacterial meningitis in neonates and children. Each pathogen produces a pore-forming cytolytic toxin, b-hemolysin/cytolysin (β-h/c) by GBS and pneumolysin by SP. The aim of this study was to understand the role of these pore-forming cytotoxins, in particular of the GBS β-h/c, as potential neurotoxins in experimental neonatal meningitis. Methods. Meningitis was induced in 7- and 11-day-old rats by intracisternal injection of wild type (WT) GBS or SP and compared with isogenic β-h/c- or pneumolysin-deficient mutants, or a double mutant of SP deficient in pneumolysin and hydrogen peroxide production. Results. GBS β-h/c and SP pneumolysin contributed to neuronal damage, worsened clinical outcome and weight loss, but had no influence on the early kinetics of leukocyte influx and bacterial growth in the cerebrospinal fluid. In vitro, β-h/c-induced neuronal apoptosis occurred independently of caspase-activation and was not preventable by the broad spectrum caspase-inhibitor z-VAD-fmk. Conclusions. These data suggest that both cytolytic toxins, the GBS β-h/c and SP pneumolysin, contribute to neuronal damage in meningitis and extend the concept of a key role for bacterial pore-forming cytolysins in the pathogenesis and sequelae of neonatal meningitis.

Original languageEnglish
Pages (from-to)393-400
Number of pages8
JournalJournal of Infectious Diseases
Volume203
Issue number3
DOIs
Publication statusPublished - Feb 1 2011

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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