The three extra-cellular zinc metalloproteinases of Streptococcus pneumoniae have a different impact on virulence in mice

Observation of survival percentages over time and detection of LD50s of knock out mutants in the proteinase genes in comparison to the type 4 TIGR4 wild type strain revealed two major aspects: i) Iga and ZmpB, present in all strains of S. pneumoniae, strongly contribute to virulence in mice; (ii) ZmpC, only present in about 25% of pneumococcal strains, has a lower influence on virulence in mice.These data suggest Iga, ZmpB and ZmpC as candidate surface proteins responsible for pneumococcal infection and potentially involved in distinct stages of pneumococcal disease.Streptococcus pneumoniae is an important human pathogen responsible for community acquired pneumonia, as well as meningitis, sepsis and milder infections like otitis media [1]. The principal factors involved in the pathogenicity of S. pneumoniae are the capsule and pneumococcal surface proteins and enzymes such as PspA, PspC, neuraminidase, pneumolysin and hyaluronidase [2-4]. A characteristic feature of S. pneumoniae and other oral streptococci is the presence of large proteases (1800–2001 amino acids) on the cell surface. Except for one serine protease, these enzymes are zinc metalloproteinases and are thought of contributing to the virulence of S. pneumoniae. The published genome sequences show that S. pneumoniae possesses two to four zinc metalloproteinases depending on the strain [5-8]. The best characterized of these enzymes is Iga which cleaves human IgA1 in the hinge region [9-12]. IgA1 protease was found to be important in lung infection and sepsis following large-scale virulence factor identification studies [13,14] and in in vitro studies performed on epithelial cells [15]. IgA proteases are common to a variety of bacteria, including Streptococcus gordonii, Streptococcus sanguis, Neisseria meningitidis, Neisseria gonorrhoeae, Haemophilus influenzae, Prevotella melaninogenica, Capnocytophaga spp [10,16-18]. The second pneumococcal zinc metalloproteinase with an assigned function is ZmpC, which