Host glycan sugar-specific pathways in streptococcus pneumonia: Galactose as a key sugar in colonisation and infection

Laura Paixão, Joana Oliveira, André Veríssimo, Susana Vinga, Eva C. Lourenço, Maria Rita Lima, Morten Kjos, Jan Willem Veening, Vitor E. Fernandes, Peter W. Andrew, Hasan Yesilkaya, Ana Rute Neves

Research output: Contribution to journalArticlepeer-review

55 Citations (Scopus)

Abstract

The human pathogen Streptococcus pneumoniae is a strictly fermentative organism that relies on glycolytic metabolism to obtain energy. In the human nasopharynx S. pneumoniae encounters glycoconjugates composed of a variety of monosaccharides, which can potentially be used as nutrients once depolymerized by glycosidases. Therefore, it is reasonable to hypothesise that the pneumococcus would rely on these glycan-derived sugars to grow. Here, we identified the sugar-specific catabolic pathways used by S. pneumoniae during growth on mucin. Transcriptome analysis of cells grown on mucin showed specific upregulation of genes likely to be involved in deglycosylation, transport and catabolism of galactose, mannose and N acetylglucosamine. In contrast to growth on mannose and Nacetylglucosamine, S. pneumoniae grown on galactose re-route their metabolic pathway from homolactic fermentation to a truly mixed acid fermentation regime. By measuring intracellular metabolites, enzymatic activities and mutant analysis, we provide an accurate map of the biochemical pathways for galactose, mannose and N-acetylglucosamine catabolism in S. pneumoniae. Intranasal mouse infection models of pneumococcal colonisation and disease showed that only mutants in galactose catabolic genes were attenuated. Our data pinpoint galactose as a key nutrient for growth in the respiratory tract and highlights the importance of central carbon metabolism for pneumococcal pathogenesis.

Original languageEnglish
Article numbere0121042
JournalPLoS ONE
Volume10
Issue number3
DOIs
Publication statusPublished - 31 Mar 2015

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