Mucosal Infections and Invasive Potential of Nonencapsulated <i>Streptococcus pneumoniae</i> Are Enhanced by Oligopeptide Binding Proteins AliC and AliD.
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Download: mBio-2018-Bradshaw-.pdf (2909.24 [Ko])
State: Public
Version: Final published version
State: Public
Version: Final published version
Serval ID
serval:BIB_CEE26F5E7C5C
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Mucosal Infections and Invasive Potential of Nonencapsulated <i>Streptococcus pneumoniae</i> Are Enhanced by Oligopeptide Binding Proteins AliC and AliD.
Journal
mBio
ISSN
2150-7511 (Electronic)
Publication state
Published
Issued date
16/01/2018
Peer-reviewed
Oui
Volume
9
Number
1
Pages
e02097-17
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Publication Status: epublish
Abstract
Nonencapsulated <i>Streptococcus pneumoniae</i> (NESp) is an emerging human pathogen that colonizes the nasopharynx and is associated with noninvasive diseases such as otitis media (OM), conjunctivitis, and nonbacteremic pneumonia. Since capsule expression was previously thought to be necessary for establishment of invasive pneumococcal disease (IPD), serotype-specific polysaccharide capsules are targeted by currently licensed pneumococcal vaccines. Yet, NESp expressing oligopeptide binding proteins AliC and AliD have been isolated during IPD. Thus, we hypothesize AliC and AliD are major NESp virulence determinants that facilitate persistence and development of IPD. Our study reveals that NESp expressing AliC and AliD have intensified virulence compared to isogenic mutants. Specifically, we demonstrate AliC and AliD enhance murine nasopharyngeal colonization and pulmonary infection and are required for OM in a chinchilla model. Furthermore, AliC and AliD increase pneumococcal survival in chinchilla whole blood and aid in resistance to killing by human leukocytes. Comparative proteome analysis revealed significant alterations in protein levels when AliC and AliD were absent. Virulence-associated proteins, including a pneumococcal surface protein C variant (CbpAC), were significantly downregulated, while starvation response indicators were upregulated in the double mutant relative to wild-type levels. We also reveal that differentially expressed CbpAC was essential for NESp adherence to epithelial cells, virulence during OM, reduction of C3b deposition on the NESp surface, and binding to nonspecific IgA. Altogether, the rise in NESp prevalence urges the need to understand how NESp establishes disease and persists in a host. This study highlights the roles of AliC, AliD, and CbpAC in the pathogenesis of NESp. <b>IMPORTANCE</b> Despite the effective, widespread use of licensed pneumococcal vaccines over many decades, pneumococcal infections remain a worldwide burden resulting in high morbidity and mortality. NESp subpopulations are rapidly rising in the wake of capsule-targeted vaccine strategies, yet there is very little knowledge on NESp pathogenic potential and virulence mechanisms. Although NESp lacks a protective capsule, NESp lineages expressing AliC and AliD have been associated with systemic infections. Furthermore, higher antibiotic resistance rates and transformation efficiencies associated with emerging NESp threaten treatment strategies needed to control pneumococcal infections and transmission. Elucidating how NESp survives within a host and establishes disease is necessary for development of broadened pneumococcal prevention methods. Our study identifies virulence determinants and host survival mechanisms employed by NESp with a high pathogenic potential. Moreover, our study also identifies virulence determinants shared by NESp and encapsulated strains that may serve as broad prevention and therapeutic targets.
Keywords
NESp, S. pneumoniae, Streptococcus pneumoniae, colonization, nonencapsulated, otitis media, pneumococcal invasive disease, pneumococcus, virulence factors
Pubmed
Web of science
Open Access
Yes
Create date
09/04/2018 13:42
Last modification date
21/11/2022 9:12