Choline-Binding Proteins

Abstract

Pneumococci covalently link phosphorylcholine to teichoic and lipoteichoic acids found in the peptidoglycan and cytoplasmic membrane, respectively. The functions of most of the choline-binding proteins (CBPs) are unknown, but a few have been studied in some depth and it is apparent that they have a role in pathogenesis and can be protective immunogens. The presence of choline-binding domains implies that any protein expressing these domains is secreted, since choline is a constituent of teichoic and lipoteichoic acids, which are cell surface polymers. The major pneumococcal autolysin LytA contains four to six choline-binding domains but is not found in eluates of pneumococcal strain Rx1 incubated with choline-containing buffers. Pneumococcal CBPs have been shown to play a role in pathogenesis in various murine models of disease. It is likely that there is some redundancy in the function of CBPs, and this, along with the large effect of the pneumococcal capsule, may explain why more is not known about the function of CBPs in pneumococcal disease. PspA and PspC are the two most well-characterized CBPs in terms of their biological functions and roles in disease. While these two proteins can be considered paralogs based on sequence homology, they make distinct contributions to pneumococcal virulence. The major autolysin of pneumococci, designated LytA, is known to be important in remodeling the cell wall of dividing pneumococci and is the common final point for many processes which lead to cell lysis.