Amino acid changes affecting the activity of pneumolysin alter the behaviour of pneumococci in pneumonia

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Following in Real Time the Impact of Pneumococcal Virulence Factors in an Acute Mouse Pneumonia Model Using Bioluminescent Bacteria
11:32

Following in Real Time the Impact of Pneumococcal Virulence Factors in an Acute Mouse Pneumonia Model Using Bioluminescent Bacteria

Published on: February 23, 2014

J E Alexander1, A M Berry, J C Paton

  • 1Department of Microbiology and Immunology, University of Leicester, Leicester, LE1 9HN, U.K.

Microbial Pathogenesis
|May 30, 1998
PubMed

Insights

Pneumolysin, a Streptococcus pneumoniae toxin, has cytotoxic and complement-activating activities. Complement activation by pneumolysin significantly impacts lung behavior and bacteremia in mice during early infection.

Area of Science:

  • Microbiology
  • Immunology
  • Toxicology

Background:

  • Streptococcus pneumoniae causes pneumonia and bacteremia.
  • Pneumolysin is a key toxin produced by S. pneumoniae.
  • Pneumolysin exhibits both cytotoxic and complement-activating functions.

Purpose of the Study:

  • To investigate the distinct roles of pneumolysin's cytotoxic and complement-activating activities in S. pneumoniae virulence.
  • To determine which pneumolysin function is more critical for early infection outcomes in a mouse model.

Main Methods:

  • Generation of isogenic mutants of S. pneumoniae with altered pneumolysin activities.
  • Intranasal infection of mice with wild-type and mutant strains.
  • Assessment of bronchopneumonia, bacteremia, and bacterial behavior in the lungs.

Main Results:

  • Reducing either cytotoxic or complement-activating activity decreased pneumococcal virulence.
  • Complement activation by pneumolysin was found to be the primary driver of early lung pathology and bacteremia.
  • The effect of complement activation on virulence was most pronounced within the first 24 hours post-infection.

Conclusions:

  • Pneumolysin's complement-activating function is critical for the early stages of S. pneumoniae infection.
  • Targeting pneumolysin's complement activation may be a viable strategy to combat pneumococcal disease.

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