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Exploring metal availability in the natural niche of Streptococcus pneumoniae to discover potential vaccine antigens.

Authors
  • van Beek, Lucille F1, 2
  • Surmann, Kristin3
  • van den Berg van Saparoea, H Bart4
  • Houben, Diane4
  • Jong, Wouter S P4
  • Hentschker, Christian3
  • Ederveen, Thomas H A5
  • Mitsi, Elena6
  • Ferreira, Daniela M6
  • van Opzeeland, Fred1, 2
  • van der Gaast-de Jongh, Christa E1, 2
  • Joosten, Irma1
  • Völker, Uwe3
  • Schmidt, Frank3, 7
  • Luirink, Joen4, 8
  • Diavatopoulos, Dimitri A1, 2
  • de Jonge, Marien I1, 2
  • 1 Section Pediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences , Nijmegen, The Netherlands. , (Netherlands)
  • 2 Radboud Center for Infectious Diseases , Nijmegen, The Netherlands. , (Netherlands)
  • 3 Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald , Greifswald, Germany. , (Germany)
  • 4 Abera Bioscience AB , Solna, Sweden. , (Sweden)
  • 5 Center for Molecular and Biomolecular Informatics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center , Nijmegen, The Netherlands. , (Netherlands)
  • 6 Liverpool School of Tropical medicine, Respiratory Infection Group , Liverpool, United Kingdom of Great Britain and Northern Ireland. , (United Kingdom)
  • 7 Proteomics Core, Weill Cornell Medicine-Qatar , Doha, Qatar. , (Qatar)
  • 8 Department of Molecular Microbiology, Faculty of Science, Amsterdam Institute of Molecular and Life Sciences, Vrije Universiteit Amsterdam , Amsterdam, The Netherlands. , (Netherlands)
Type
Published Article
Journal
Virulence
Publisher
Landes Bioscience
Publication Date
Dec 01, 2020
Volume
11
Issue
1
Pages
1310–1328
Identifiers
DOI: 10.1080/21505594.2020.1825908
PMID: 33017224
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Nasopharyngeal colonization by Streptococcus pneumoniae is a prerequisite for pneumococcal transmission and disease. Current vaccines protect only against disease and colonization caused by a limited number of serotypes, consequently allowing serotype replacement and transmission. Therefore, the development of a broadly protective vaccine against colonization, transmission and disease is desired but requires a better understanding of pneumococcal adaptation to its natural niche. Hence, we measured the levels of free and protein-bound transition metals in human nasal fluid, to determine the effect of metal concentrations on the growth and proteome of S. pneumoniae. Pneumococci cultured in medium containing metal levels comparable to nasal fluid showed a highly distinct proteomic profile compared to standard culture conditions, including the increased abundance of nine conserved, putative surface-exposed proteins. AliA, an oligopeptide binding protein, was identified as the strongest protective antigen, demonstrated by the significantly reduced bacterial load in a murine colonization and a lethal mouse pneumonia model, highlighting its potential as vaccine antigen.

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