Novel surface attachment mechanism of the Streptococcus pneumoniae protein PspA

Pneumococcal surface protein A (PspA) of Streptococcus pneumoniae has been found to utilize a novel mechanism for anchoring to the bacterial cell surface. In contrast to that of surface proteins from other gram-positive bacteria, PspA anchoring required choline-mediated interactions between the membrane-associated lipoteichoic acid and the C-terminal repeat region of PspA. Release of PspA from the cell surface could be effected by deletion of 5 of the 10 C-terminal repeat units, by high concentrations of choline, or by growth in choline-deficient medium. Other pneumococcal proteins, including autolysin, which has a similar C-terminal repeat region, were not released by these treatments. The attachment mechanism utilized by PspA thus appears to be uniquely adapted to exploit the unusual structure of the pneumococcal cell surface. Further, it has provided the means for rapid and simple isolation of immunogenic PspA from S. pneumoniae. Surface proteins from many gram-positive bacteria contain a common C-terminal motif consisting of a proline-rich region, the amino acid sequence LPXTGX, a highly hydrophobic membrane-spanning region of 16 to 20 amino acids, and a charged stop-transfer tail of 4 to 7 amino acids at the C terminus (21). This motif, which appears to be important i