Pneumococcal surface proteins: when the whole is greater than the sum of its parts

Abstract

Surface-exposed proteins of pathogenic bacteria are considered as potential virulence factors through their direct contribution to host-pathogen interactions. Four families of surface proteins decorate the cell surface of the human pathogen Streptococcus pneumoniae. Besides lipoproteins and LPXTG proteins, also present in other gram-positive bacteria, the pneumococcus presents the choline-binding protein (CBP) family and the non-classical surface proteins (NCSPs). The CBPs present specific structural features that allow their anchorage to the cell envelope through non-covalent interaction with choline residues of lipoteichoic acid and teichoic acid. NCSP is an umbrella term for less characterized proteins displaying moonlighting functions on the pneumococcal surface that lack a leader peptide and membrane-anchor motif. Considering the unceasing evolution of microbial species under the selective pressure of antibiotic use, detailed understanding of the interaction between pathogen and the host cells is required for the development of novel therapeutic strategies to combat pneumococcal infections. This article reviews recent progress in the investigation of the three-dimensional structures of surface-exposed pneumococcal proteins. The modular nature of some of them produces a great versatility and sophistication of the virulence functions that, in most cases, cannot be deduced by the structural analysis of the isolated modules.

Conformational Analysis of the Streptococcus pneumoniae Hyaluronate Lyase and Characterization of Its Hyaluronan-specific Carbohydrate-binding Module

“…Among these molecules involved in the bacterium-host interaction are a wide variety of proteins that are covalently and non-covalently attached to the bacterial surface (47, 48). Carbohydrate-active enzymes are well represented among these proteins and are often associated with pneumococcal virulence, as is the case with Hyl.…”

How Listeria monocytogenes organizes its surface for virulence

“…The protein is then transferred to its final acceptor, lipid II (peptidoglycan precursor), which establishes a new bond between the amine group of a cross-bridge residue ( meso -diaminopimelic acid in L. monocytogenes ) and the C-terminal threonine carboxyl group of the surface protein (Ton-That et al, 1997). Proteins with LPXTG motifs are found in a multiplicity of Gram-positive organisms (Navarre and Schneewind, 1999; Mazmanian et al, 2001; Hendrickx et al, 2009; Pérez-Dorado et al, 2012). L. monocytogenes stands out as the species with the largest number, encoding 41 proteins (over 1% of its genome) (Glaser et al, 2001; Cabanes et al, 2002), seven of which are currently described as virulence factors.…”

Modular Architecture and Unique Teichoic Acid Recognition Features of Choline-Binding Protein L (CbpL) Contributing to Pneumococcal Pathogenesis

“…The latter two are decorated with phosphorylcholine (PCho) residues. Besides lipoproteins, sortase-anchored LPxTG proteins and surface-exposed moonlighting proteins that exist in other Gram-positive bacteria, the pneumococcus displays Choline-Binding Proteins (CBPs)4.…”