Diverse evolutionary patterns of pneumococcal antigens identified by pangenome-wide immunological screening

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Title: Diverse evolutionary patterns of pneumococcal antigens identified by pangenome-wide immunological screening
Author(s): Croucher, NJ
Campo, JJ
Le, TQ
Liang, X
Bentley, SD
Hanage, WP
Lipsitch, M
Item Type: Journal Article
Abstract: Characterizing the immune response to pneumococcal proteins is critical in understanding this bacterium’s epidemiology and vaccinology. Probing a custom-designed proteome microarray with sera from 35 healthy US adults revealed a continuous distribution of IgG affinities for 2,190 potential antigens from the species-wide pangenome. Reproducibly elevated IgG binding was elicited by 208 “antibody binding targets” (ABTs), which included 109 variants of the diverse pneumococcal surface proteins A and C (PspA and PspC) and zinc metalloprotease A and B (ZmpA and ZmpB) proteins. Functional analysis found ABTs were enriched in motifs for secretion and cell surface association, with extensive representation of cell wall synthesis machinery, adhesins, transporter solute-binding proteins, and degradative enzymes. ABTs were associated with stronger evidence for evolving under positive selection, although this varied between functional categories, as did rates of diversification through recombination. Particularly rapid variation was observed at some immunogenic accessory loci, including a phage protein and a phase-variable glycosyltransferase ubiquitous among the diverse set of genomic islands encoding the serine-rich PsrP glycoprotein. Nevertheless, many antigens were conserved in the core genome, and strains’ antigenic profiles were generally stable. No strong evidence was found for any epistasis between antigens driving population dynamics, or redundancy between functionally similar accessory ABTs, or age stratification of antigen profiles. These results highlight the paradox of why substantial variation is observed in only a subset of epitopes. This result may indicate only some interactions between immunoglobulins and ABTs clear pneumococcal colonization or that acquired immunity to pneumococci is an accumulation of individually weak responses to ABTs evolving under different levels of functional constraint.
Publication Date: 4-Jan-2017
Date of Acceptance: 5-Dec-2016
URI: http://hdl.handle.net/10044/1/45263
DOI: https://dx.doi.org/10.1073/pnas.1613937114
ISSN: 0027-8424
Publisher: National Academy of Sciences
Start Page: E357
End Page: E366
Journal / Book Title: Proceedings of the National Academy of Sciences
Volume: 114
Issue: 3
Copyright Statement: © 2017 National Academy of Sciences.
Sponsor/Funder: Wellcome Trust
Funder's Grant Number: 104169/Z/14/Z
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
genomics
pathogens
evolution
immunology
epidemiology
STREPTOCOCCUS-PNEUMONIAE
CONJUGATE VACCINE
SURFACE PROTEIN
NASOPHARYNGEAL CARRIAGE
PHYLOGENETIC ANALYSIS
MAXIMUM-LIKELIHOOD
ANTIBODY-RESPONSES
ACQUIRED-IMMUNITY
INFECTIOUS AGENTS
STRAIN STRUCTURE
epidemiology
evolution
genomics
immunology
pathogens
MD Multidisciplinary
Publication Status: Published
Appears in Collections:Faculty of Medicine
Epidemiology, Public Health and Primary Care



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