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

Virulence

Wouter S. P. Jong¹  H. Bart van den Berg van Saparoea¹  Diane Houben¹  Joen Luirink²  Thomas H. A. Ederveen³  Christian Hentschker⁴  Uwe Völker⁴  Kristin Surmann⁴  Frank Schmidt⁵  Elena Mitsi⁶  Daniela M. Ferreira⁶  Irma Joosten⁷  Dimitri A. Diavatopoulos⁸  Lucille F. van Beek⁸  Fred van Opzeeland⁸  Christa E. van der Gaast – de Jongh⁸  Marien I. de Jonge⁸ 

[1] Abera Bioscience AB, Solna, Swede;Abera Bioscience AB, Solna, Swede;Department of Molecular Microbiology, Faculty of Science, Amsterdam Institute of Molecular and Life Sciences, Vrije Universiteit Amsterdam, Amsterdam, The Netherland;Center for Molecular and Biomolecular Informatics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherland;Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, German;Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, German;Proteomics Core, Weill Cornell Medicine-Qatar, Doha, Qata;Liverpool School of Tropical medicine, Respiratory Infection Group, Liverpool, United Kingdom of Great Britain and Northern Irelan;Section Pediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherland;Section Pediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherland;Radboud Center for Infectious Diseases, Nijmegen, The Netherland;

关键词: Streptococcus pneumoniae;    transition metals;    nasal fluid;    protein antigens;    colonization;    in vivo;   

DOI  :  10.1080/21505594.2020.1825908

来源: Taylor & Francis

【 摘 要 】

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.

【 授权许可】

CC BY