Cellular interactions by LPxTG-anchored pneumococcal adhesins and their streptococcal homologues

Abstract

SummaryIn this review we focus on three important families of LPxTG-anchored adhesins in the human pathogen Streptococcus pneumoniae, but also their homologues in related streptococci. We discuss the contribution of these streptococcal adhesins to host tropism, pathogenesis and their interactions with different host cell types. The first surface structures discussed are the heteropolymeric pili that have been found in important streptococcal pathogens such as S. pneumoniae, S. pyogenes, S. agalactiae and E. faecalis/faecium. Major and minor pilus subunit proteins are covalently joined and finally attached to the cell wall through the action of specific sortases. The role of pili and individual pilin subunits in adhesion and pathogenesis and their structure and assembly in different streptococcal species are being covered. Furthermore, we address recent findings regarding a family of large glycosylated serine-rich repeat (SRR) proteins that act as fibrillar adhesins for which homologues have been found in several streptococcal species including pneumococci. In the pneumococcal genome both pili and its giant SRR protein are encoded by accessory genes present in particular clonal lineages for which epidemiological information is available. Finally, we briefly discuss the role played by the pneumococcal neuraminidase NanA in adhesion and pathogenesis.

Molecular characterization of pneumococcal surface protein K, a potential pneumococcal vaccine antigen

“…Its N-terminal and Cterminal ends encode a conserved secretion signal motif and a LPxTG motif for secreting and anchoring on the peptidoglycan layer, respectively. 20 Previous studies have shown that PspK mediates the binding of NESp to human lung epithelial cells and nasopharyngeal colonization in mice. 21 In addition, the expression of PspK in NCC1 has been shown to be critical for the development of AOM in a pneumococcal AOM model in chinchillas.…”

Streptococcus pneumoniae Endopeptidase O (PepO) Is a Multifunctional Plasminogen- and Fibronectin-binding Protein, Facilitating Evasion of Innate Immunity and Invasion of Host Cells

“…Surface proteins like choline-binding proteins, LPXTG motif containing proteins and lipoproteins (7)(8)(9), have been described as ligands for cellular receptors and binding molecules interacting with various components of the extracellular matrix (ECM) 3 or serum proteins of the host. For example, pneumococcal surface protein C (PspC) is a multifunctional choline-binding protein and a major virulence factorof pneumococci that interacts directly and in a human-specific manner with the polymeric immunoglobulin receptor, and mediates pneumococcal adherence and invasion of host cells (10 -12).…”

The Pneumococcus: Epidemiology, Microbiology, and Pathogenesis

“…PCho serves as a docking station for noncovalent linkage of many pneumococcal proteins to the bacterial surface (Rosenow et al 1997). In addition, the LPxTG motif is targeted by sortases that covalently link proteins to the cell wall (Löfling et al 2011).…”