Pneumococcal zinc metalloproteinase ZmpC cleaves human matrix metalloproteinase 9 and is a virulence factor in experimental pneumonia

Mol Microbiol. 2003 Aug;49(3):795-805. doi: 10.1046/j.1365-2958.2003.03596.x.

Abstract

The ZmpC zinc metalloproteinase of Streptococcus pneumoniae, annotated in the type 4 genome as SP0071, was found to cleave human matrix metalloproteinase 9 (MMP-9). The previously described IgA protease activity was confirmed to be specifically linked to the IgA1-protease/SP1154 zinc metalloproteinase. MMP-9 is a protease cleaving extracellular matrix gelatin and collagen and is activated by proteolytic cleavage like most proteases. MMP-9 is a human protease and is involved in a variety of physiological and pathological matrix degrading processes, including tissue invasion of metastases and opening of the blood-brain barrier. While TIGR4 (serotype 4) and G54 (serotype 19) pneumococcal genome strains have a highly conserved copy of zmpC, the genome of R6 (a derivative of serotype 2 D39 strain) lacks zmpC. Both the analysis for zmpC presence and MMP-9 cleavage activity in various pneumococcal strains showed correlation of ZmpC with MMP-9 cleavage activity. When assaying clinical isolates of S. pneumoniae, the zmpC gene was not found in any of the nasal and conjunctival swab isolates, but it was present in 1 out of 13 meningitis isolates and in 6 out of 11 pneumonia isolates. In a murine pneumonia model, infection with a zmpC-mutant reduced mortality at 3-4 days post-infection by 75%, when compared with infection with wild-type strains. These data indicate that the ZmpC pneumococcal protease may play a role in pneumococcal virulence and pathogenicity in the lung.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Animals
  • Blood-Brain Barrier
  • Body Fluids / microbiology
  • Extracellular Matrix / metabolism
  • Female
  • Gene Targeting
  • Genotype
  • Humans
  • Lung / enzymology
  • Lung / microbiology
  • Matrix Metalloproteinase 9 / metabolism*
  • Meningitis, Pneumococcal / enzymology
  • Meningitis, Pneumococcal / microbiology
  • Metalloendopeptidases / genetics
  • Metalloendopeptidases / physiology*
  • Mice
  • Phenotype
  • Pneumonia, Pneumococcal / enzymology
  • Pneumonia, Pneumococcal / microbiology*
  • Serine Endopeptidases / physiology
  • Species Specificity
  • Streptococcus pneumoniae / classification
  • Streptococcus pneumoniae / enzymology*
  • Streptococcus pneumoniae / isolation & purification
  • Streptococcus pneumoniae / pathogenicity
  • Virulence

Substances

  • ZmpB enzyme
  • Serine Endopeptidases
  • IgA-specific serine endopeptidase
  • Metalloendopeptidases
  • ZmpC protein, Streptococcus pneumoniae
  • Matrix Metalloproteinase 9