title: Characterisation of an oxidative response inhibitor produced by Streptococcus pneumoniae.
abstract: BACKGROUND
  Pneumonia caused by infection with Streptococcus pneumoniae is still a major clinical problem. Reactive oxygen species contribute to the killing of these bacteria by polymorphonuclear leucocytes (PMNs). Defence mechanisms of Str pneumoniae which counter reactive oxygen species are characterised.
  
  
  METHODS
  PMNs were stimulated with phorbol myristate acetate (PMA) in the presence and absence of Str pneumoniae and supernatants from them, and superoxide (O2-) production was measured by the reduction of ferricytochrome c.
  
  
  RESULTS
  Streptococcus pneumoniae, but not Klebsiella pneumoniae or Staphylococcus aureus, inhibited PMA stimulated superoxide production by PMNs. Washed PMNs which had been preincubated with Str pneumoniae autolysis phase supernatants also exhibited depressed H2O2 production in response to PMA. The inhibitory activity was not attributable to non-specific cytotoxicity as assessed by release of the cytoplasmic enzyme lactate dehydrogenase, nor did the supernatants inhibit PMA stimulated degranulation of PMNs. Fractionation of the autolysis phase supernatants revealed inhibitory activity in both the fractions greater than and less than 10 kD. Like pneumolysin the inhibitory activity was heat sensitive. However, both a parent and pneumolysin negative mutant Str pneumoniae, and autolysis phase supernatants from them, inhibited PMN superoxide production. Antisera to pneumolysin failed to abrogate the inhibitory effect of intact Str pneumoniae or autolysis phase supernatants from types 1 or 14 Str pneumoniae.
  
  
  CONCLUSIONS
  The inhibitory effect of Str pneumoniae on the respiratory burst of PMNs is not shared by two other common lung pathogens. The existence of a novel inhibitor of the PMN respiratory burst, distinct from pneumolysin, has been demonstrated. The inhibitor is specific for the respiratory burst and is active both in the logarithmic phase of growth and during autolysis.
authors.affiliation: Department of Pathology and Microbiology, University of Bristol.
authors.forename: F E
authors.initials: FE
authors.lastname: Perry
authors.forename: C J
authors.initials: CJ
authors.lastname: Elson
authors.forename: T J
authors.initials: TJ
authors.lastname: Mitchell
authors.forename: P W
authors.initials: PW
authors.lastname: Andrew
authors.forename: J R
authors.initials: JR
authors.lastname: Catterall
mesh_terms: D001329:Autolysis; D001426:Bacterial Proteins; D003603:Cytotoxins / Q000276:immunology; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D007711:Klebsiella pneumoniae / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D016897:Respiratory Burst; D013211:Staphylococcus aureus / Q000378:metabolism; D013268:Stimulation, Chemical; D013296:Streptococcus pneumoniae / Q000378:metabolism* / Q000472:pathogenicity; D013301:Streptolysins / Q000276:immunology; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D001426:Bacterial Proteins; D003603:Cytotoxins; D007106:Immune Sera; D017382:Reactive Oxygen Species; D013301:Streptolysins; C032290:plY protein, Streptococcus pneumoniae; D013481:Superoxides; D013755:Tetradecanoylphorbol Acetate