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The role of the exopolyphosphatase PPX in avoidance by Neisseria meningitidis of complement-mediated killing

Qian Zhang1, Yanwen Li, Christoph M Tang

  • 1Department of Microbiology, Centre for Molecular Microbiology and Infection, Flowers Building, Imperial College London, London SW7 2AZ, United Kingdom.

The Journal of Biological Chemistry
|August 26, 2010
PubMed

Insights

Neisseria meningitidis mutants lacking exopolyphosphatase (PPX) show increased resistance to complement-mediated killing. PPX activity is crucial for bacterial interaction with the complement system, impacting immunity.

Area of Science:

  • Microbiology
  • Immunology
  • Biochemistry

Background:

  • The complement system is vital for defense against Neisseria meningitidis.
  • Neisseria meningitidis is a significant human pathogen.

Purpose of the Study:

  • To investigate the role of exopolyphosphatase (PPX) in Neisseria meningitidis resistance to complement.
  • To identify key amino acids in PPX essential for its biochemical activity and complement interaction.

Main Methods:

  • Isolation and characterization of a meningococcal mutant lacking PPX.
  • Site-directed mutagenesis to define essential amino acids in PPX.
  • Assays to assess bacterial resistance to complement-mediated killing and interaction with complement pathways.

Main Results:

  • A meningococcal mutant lacking PPX exhibited enhanced resistance to complement-mediated killing.
  • Specific amino acids, including Glu(117) and Walker B box residues, were identified as critical for PPX biochemical activity.
  • PPX biochemical activity was necessary for interaction with the complement system.
  • The resistance of the ppx mutant was not due to alterations in known evasion structures like capsule or LPS.
  • PPX expression was shown to modulate Neisseria meningitidis interactions with the alternative complement pathway.

Conclusions:

  • Exopolyphosphatase (PPX) plays a significant role in Neisseria meningitidis's interaction with the complement system.
  • The biochemical activity of PPX is essential for this interaction, independent of major surface structures.
  • Understanding PPX function offers insights into meningococcal pathogenesis and potential therapeutic targets.

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