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

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posted on 05.10.2020, 21:00 authored by 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

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.

Funding

This study was supported by ‘NWO TTW Perspectief Programma’, ‘A technology center for Bacterial Vaccines (BacVactory)’ P14-P15 Project 1 Antigen discovery (MIdJ) and P14-15 Project 3T Antigen Display (JL). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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