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

Autor: van Beek, Lucille F., Surmann, Kristin, van den Berg van Saparoea, H. Bart, Houben, Diane, Jong, Wouter S. P., Hentschker, Christian, Ederveen, Thomas H. A., Mitsi, Elena, Ferreira, Daniela M., van Opzeeland, Fred, van der Gaast – de Jongh, Christa E., Joosten, Irma, Völker, Uwe, Schmidt, Frank, Luirink, Joen, Diavatopoulos, Dimitri A., de Jonge, Marien I.
Zdroj: Virulence; December 2020, Vol. 11 Issue: 1 p1310-1328, 19p
Abstrakt: ABSTRACTNasopharyngeal colonization by Streptococcus pneumoniaeis 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.
Databáze: Supplemental Index