AUTHOR=Lane Jessica R. , Tata Muralidhar , Briles David E. , Orihuela Carlos J. 

TITLE=A Jack of All Trades: The Role of Pneumococcal Surface Protein A in the Pathogenesis of Streptococcus pneumoniae

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=Volume 12 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2022.826264

DOI=10.3389/fcimb.2022.826264

ISSN=2235-2988

ABSTRACT=Streptococcus pneumoniae (Spn), or the pneumococcus, is a Gram-positive bacterium that colonizes the upper airway. Spn is an opportunistic pathogen capable of life-threatening disease should it become established in the lungs, gain access to the bloodstream, or disseminate to vital organs including the central nervous system. Spn is encapsulated, allowing it to avoid phagocytosis, and current preventative measures against infection include polyvalent vaccines composed of capsular polysaccharide corresponding to its deadliest serotypes. The pneumococcus also has a plethora of surface components that allow the bacteria to adhere to host cells, facilitate the evasion of the immune system, and obtain vital nutrients; one family of these are the choline-binding proteins (CBPs). CBPs are surface exposed and non-covalently bound to phosphorylcholine (PC) residues on teichoic and lipoteichoic acid. Pneumococcal surface protein A (PspA) is one of the most abundant CBPs and confers protection against the host by inhibiting recognition by C-reactive protein and neutralizing the antimicrobial peptide lactoferricin. Recently our group has identified two new roles for PspA: co-opting of host lactate dehydrogenase to enhance lactate availability and binding to dying host cells via host-cell bound glyceraldehyde 3-phosphate dehydrogenase. These properties have been shown to influence Spn localization and virulence in the lower airway. Herein we review the impact of CBPs, and in particular PspA, on pneumococcal pathogenesis. We discuss the potential and limitations of using PspA as a conserved vaccine antigen in a conjugate vaccine formulation and the function PspA may have in transmission given its newly defined properties. PspA is a vital component of the pneumococcal virulence arsenal – therefore, understanding the molecular aspects of PspA is essential in clarifying its potential as a new target for treating and preventing pneumococcal pneumonia.