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

Lucille F. van Beek*, Kristin Surmann, H. Bart van den Berg van Saparoea, Diane Houben, Wouter S.P. Jong, Christian Hentschker, Thomas H.A. Ederveen, Elena Mitsi, Daniela M. Ferreira, Fred van Opzeeland, Christa E. van der Gaast–de Jongh, Irma Joosten, Uwe Völker, Frank Schmidt, Joen Luirink, Dimitri A. Diavatopoulos, Marien I. de Jonge

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)1310-1328
Number of pages19
JournalVirulence
Volume11
Issue number1
DOIs
Publication statusPublished - 5 Oct 2020

Keywords

  • colonization
  • in vivo-mimicking
  • nasal fluid
  • protein antigens
  • Streptococcus pneumoniae
  • transition metals

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