Molecular analyses identifies new domains and structural differences among Streptococcus pneumoniae immune evasion proteins PspC and Hic

Shanshan Du,Cláudia Vilhena,Alfredo Sahagún-Ruiz,Sven Hammerschmidt,Samantha King,Christine Skerka,Peter F Zipfel

doi:10.1038/s41598-020-79362-3

Shanshan Du, Cláudia Vilhena + Show 5 more

Open Access

https://doi.org/10.1038/s41598-020-79362-3

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Abstract

The PspC and Hic proteins of Streptococcuspneumoniae are some of the most variable microbial immune evasion proteins identified to date. Due to structural similarities and conserved binding profiles, it was assumed for a long time that these pneumococcal surface proteins represent a protein family comprised of eleven subgroups. Recently, however, the evaluation of more proteins revealed a greater diversity of individual proteins. In contrast to previous assumptions a pattern evaluation of six PspC and five Hic variants, each representing one of the previously defined subgroups, revealed distinct structural and likely functionally regions of the proteins, and identified nine new domains and new domain alternates. Several domains are unique to PspC and Hic variants, while other domains are also present in other virulence factors encoded by pneumococci and other bacterial pathogens. This knowledge improved pattern evaluation at the level of full-length proteins, allowed a sequence comparison at the domain level and identified domains with a modular composition. This novel strategy increased understanding of individual proteins variability and modular domain composition, enabled a structural and functional characterization at the domain level and furthermore revealed substantial structural differences between PspC and Hic proteins. Given the exceptional genomic diversity of the multifunctional PspC and Hic proteins a detailed structural and functional evaluation need to be performed at the strain level. Such knowledge will also be useful for molecular strain typing and characterizing PspC and Hic proteins from new clinical S. pneumoniae strains.

Highlights

We do not know exactly which domain(s) are integrated into the bacterial cell wall, which domain(s) span the capsule and which domains are externally positioned. The heterogeneity among these important immune evasion proteins, we aimed to evaluate the structure and domain composition of six PspC and five Hic variants, each representing one of the clusters defined by Ianelli et al.[40]
The selected proteins vary in size and mass, with PspC1.1 being the largest protein with a length of 929 aa and a molecular mass of 110 kDa, while Hic/PspC8.1 is the smallest protein with a length of 503 aa and a mass of 65 kDa (Supplementary Table I)
Evaluating the domain composition of selected PspC and Hic variants and an in-depth characterization of the domain composition advanced our understanding of the structure of these virulence determinants

Summary

Introduction

Vaccines protecting against a higher number of serotypes or a serotype-independent vaccine is needed to combat the pathogen efficiently These limitations make it important to identify new virulence determinants that may serve as novel vaccine or therapeutic targets, to understand the diversity of these determinants and to define the immune escape strategies of this pathogenic b acterium[1,11,12]. Because the patterns of domains are not exactly known and the borders of individual domains are not well-defined, a straightforward system of variant designation is at present difficult to achieve This makes assignment of existing and newly identified pspC and hic genes, including those from novel clinical pneumococcal isolates, difficult or even impossible[27]

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