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

doi:10.1080/21505594.2020.1825908

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 Journal › Article › Academic › peer-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 language	English
Pages (from-to)	1310-1328
Number of pages	19
Journal	Virulence
Volume	11
Issue number	1
DOIs	https://doi.org/10.1080/21505594.2020.1825908
Publication status	Published - 5 Oct 2020

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. We thank Stephan Michalik for supporting the proteomics data visualization (Shiny App) and Paul van der Ven for performing the ICP-MS measurements.

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1080/21505594.2020.1825908

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van Beek, L. F., Surmann, K., van den Berg van Saparoea, H. B., Houben, D., Jong, W. S. P., Hentschker, C., Ederveen, T. H. A., Mitsi, E., Ferreira, D. M., van Opzeeland, F., van der Gaast–de Jongh, C. E., Joosten, I., Völker, U., Schmidt, F., Luirink, J., Diavatopoulos, D. A., & de Jonge, M. I. (2020). Exploring metal availability in the natural niche of Streptococcus pneumoniae to discover potential vaccine antigens. Virulence, 11(1), 1310-1328. https://doi.org/10.1080/21505594.2020.1825908

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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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van Beek, LF, Surmann, K, van den Berg van Saparoea, HB, Houben, D, Jong, WSP, Hentschker, C, Ederveen, THA, Mitsi, E, Ferreira, DM, van Opzeeland, F, van der Gaast–de Jongh, CE, Joosten, I, Völker, U, Schmidt, F, Luirink, J, Diavatopoulos, DA & de Jonge, MI 2020, 'Exploring metal availability in the natural niche of Streptococcus pneumoniae to discover potential vaccine antigens', Virulence, vol. 11, no. 1, pp. 1310-1328. https://doi.org/10.1080/21505594.2020.1825908

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AU - van Beek, Lucille F.

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AU - van den Berg van Saparoea, H. Bart

AU - Houben, Diane

AU - Jong, Wouter S.P.

AU - Hentschker, Christian

AU - Ederveen, Thomas H.A.

AU - Mitsi, Elena

AU - Ferreira, Daniela M.

AU - van Opzeeland, Fred

AU - van der Gaast–de Jongh, Christa E.

AU - Joosten, Irma

AU - Völker, Uwe

AU - Schmidt, Frank

AU - Luirink, Joen

AU - Diavatopoulos, Dimitri A.

AU - de Jonge, Marien I.

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N2 - 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.

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

Abstract

Funding

Keywords

UN SDGs

Access to Document

Persistent URL (handle)

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