Streptococcus pneumoniae surface choline-binding proteins (CBPs) (CBPs)

Streptococcus pneumoniae surface choline-binding proteins (CBPs) are a family of 13 to 16 modular proteins that are non-covalently anchored to the phosphorylcholine residues of teichoic and lipoteichoic acids in the bacterial cell wall [asm.org, 2023; nih.gov, 2016]. These proteins are essential for the pathogen's life cycle and virulence, performing diverse functions such as cell wall remodeling (LytA, LytB, LytC), adhesion to host epithelial and endothelial cells (CbpA/PspC), and evasion of the host immune system by inhibiting complement deposition (PspA, PspC) [nih.gov, 1998; nih.gov, 2000]. Because CBPs are present in all pneumococcal strains and are surface-exposed, they are considered high-priority targets for the development of serotype-independent protein-based vaccines and novel antimicrobial therapies [nih.gov, 2016; mdpi.com, 2021]. Current therapeutic approaches include experimental vaccines utilizing recombinant PspA or PspC to elicit protective antibodies, as well as small-molecule choline analogs and phage-derived enzybiotics that disrupt protein anchoring or directly lyse the cell wall [nih.gov, 2006; nih.gov, 2015]. However, the high degree of allelic variation among certain CBPs and their presence in commensal streptococci present significant challenges for drug and vaccine design [nih.gov, 2016; nih.gov, 2002]. For instance, PspA and PspC exhibit significant sequence diversity, which may necessitate the use of multivalent formulations to ensure broad protection [nih.gov, 2015]. Additionally, the potential for immune escape through the selection of variants with altered protein sequences remains a concern for long-term efficacy [nih.gov, 2002].

Other names

Pneumococcal choline-binding proteinsCholine-binding module-containing proteinsCBM-containing proteinsPneumococcal surface protein A (PspA)Pneumococcal surface protein C (PspC)Choline-binding protein A (CbpA)Autolysin (LytA)

Therapeutic strategies targeting CBPs involve: (1) Induction of opsonophagocytic antibodies via protein vaccines to facilitate bacterial clearance and block adhesion to host tissues; (2) Competitive inhibition of the choline-binding module (CBM) by small-molecule analogs to prevent protein anchoring to the cell wall; and (3) Direct enzymatic degradation of the peptidoglycan layer by phage-derived enzybiotics (endolysins) to induce bacterial lysis [nih.gov, 2016; nih.gov, 2006; nih.gov, 2015].