Characterization of selected strains of pneumococcal surface protein A

Several proteins, in addition to the polysaccharide capsule, have recently been implicated in the full virulence of the Streptococcus pneumoniae bacte rial pathogen. One of these novel virulence factors of S. pneumoniae is pne umococcal surface protein A (PspA). The N-terminal, cell surface exposed, a nd functional part of PspA is essential for full pneumococcal virulence, as evidenced by the fact that antibodies raised against this part of the prot ein are protective against pneumococcal infections. PspA has recently been implicated in anticomplementary function as it reduces complement-mediated clearance and phagocytosis of pneumococci. Several recombinant N-terminal f ragments of PspA from different strains of pneumococci, Px1, BG9739, BG6380 , EF3296, and EF5668, were analyzed using circular dichroism, analytical ul tracentrifugation sedimentation velocity and equilibrium methods, and seque nce homology. Uniformly, all strains of PspA molecules studied have a high a-helical secondary structure content and they adopt predominantly a coiled -coil structure with an elongated, likely rod-like shape. No beta -sheet st ructures were detected for any of the PspA molecules analyzed. All PspAs we re found to be monomeric in solution with the exception of the BG9739 strai n which had the propensity to partially aggregate but only into a tetrameri c form. These structural properties were correlated with the functional, an ti-complementary properties of PspA molecules based on the polar distributi on of highly charged termini of its coiled-coil domain. The recombinant Rx1 PspA is currently under consideration for pneumococcal vaccine development .