The putative proteinase maturation protein A of Streptococcus pneumoniae is a conserved surface protein with potential to elicit protective immune responses
Surface-exposed proteins often play an important role in the interaction
between pathogenic bacteria and their host. We isolated a pool of
hydrophobic, surface-associated proteins of Streptococcus pneumoniae. The
opsonophagocytic activity of hyperimmune serum raised against this protein
fraction was high and species specific. Moreover, the opsonophagocytic
activity was independent of the capsular type and chromosomal genotype of
the pneumococcus. Since the opsonophagocytic activity is presumed to
correlate with in vivo protection, these data indicate that the protein
fraction has the potential to elicit species-specific immune protection
with cross-protection against various pneumococcal strains. Individual
proteins in the extract were purified by two-dimensional gel
electrophoresis. Antibodies raised against three distinct proteins
contributed to the opsonophagocytic activity of the serum. The proteins
were identified by mass spectrometry and N-terminal amino acid sequencing.
Two proteins were the previously characterized pneumococcal surface
protein A and oligopeptide-binding lipoprotein AmiA. The third protein was
the recently identified putative proteinase maturation protein A (PpmA),
which showed homology to members of the family of peptidyl-prolyl
cis/trans isomerases. Immunoelectron microscopy demonstrated that PpmA was
associated with the pneumococcal surface. In addition, PpmA was shown to
elicit species-specific opsonophagocytic antibodies that were
cross-reactive with various pneumococcal strains. This antibody
cross-reactivity was in line with the limited sequence variation of ppmA.
The importance of PpmA in pneumococcal pathogenesis was demonstrated in a
mouse pneumonia model. Pneumococcal ppmA-deficient mutants showed reduced
virulence. The properties of PpmA reported here indicate its potential for
inclusion in multicomponent protein vaccines
