TY - JOUR
T1 - Exploring metal availability in the natural niche of Streptococcus pneumoniae to discover potential vaccine antigens
AU - van Beek, Lucille F.
AU - Surmann, Kristin
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
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.
PY - 2020/12/1
Y1 - 2020/12/1
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.
KW - colonization
KW - in vivo-mimicking
KW - nasal fluid
KW - protein antigens
KW - Streptococcus pneumoniae
KW - transition metals
U2 - 10.1080/21505594.2020.1825908
DO - 10.1080/21505594.2020.1825908
M3 - Article
SN - 2150-5594
VL - 11
SP - 1310
EP - 1328
JO - Virulence
JF - Virulence
IS - 1
ER -
