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Periplasmic superoxide dismutase in meningococcal pathogenicity

K E Wilks1, K L Dunn, J L Farrant

  • 1Department of Paediatrics, Imperial College, School of Medicine at St. Mary's Hospital, London, United Kingdom.

Infection and Immunity
|January 10, 1998
PubMed
Summary

Neisseria meningitidis superoxide dismutase C (sodC) protects against host-derived toxic oxygen radicals. A sodC mutant demonstrated reduced virulence in a mouse model, indicating Cu,Zn SOD contributes to meningococcal pathogenicity.

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Area of Science:

  • Microbiology
  • Biochemistry
  • Pathogenesis

Background:

  • Meningococcal sodC encodes a periplasmic copper- and zinc-cofactored superoxide dismutase (Cu,Zn SOD).
  • Cu,Zn SOD detoxifies superoxide radicals, preventing harmful downstream reactions.
  • Its periplasmic location suggests a role in defending against extracellular microbicidal oxygen free radicals from host defenses.

Purpose of the Study:

  • To investigate the role of meningococcal Cu,Zn SOD in pathogenicity.
  • To determine if Cu,Zn SOD protects against exogenous superoxide radicals.

Main Methods:

  • Construction of a sodC mutant using allelic exchange.
  • Comparative growth and survival assays of wild-type and mutant meningococci in aerobic liquid culture.
  • Sensitivity testing against intracellular (paraquat) and extracellular (xanthine/xanthine oxidase) superoxide generators.

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  • Virulence assessment in a mouse intraperitoneal infection model.
  • Main Results:

    • Wild-type and mutant meningococci exhibited similar growth rates and aerobic survival.
    • The sodC mutant showed no increased sensitivity to paraquat but was 1,000-fold more sensitive to extracellularly generated superoxide.
    • The sodC mutant was significantly less virulent in the mouse infection model.

    Conclusions:

    • Meningococcal Cu,Zn SOD plays a crucial role in protecting against exogenous superoxide.
    • Periplasmic Cu,Zn SOD contributes to the virulence of Neisseria meningitidis.
    • This likely occurs by neutralizing toxic oxygen species produced by host defenses.