title: Host glycan sugar-specific pathways in Streptococcus pneumoniae: galactose as a key sugar in colonisation and infection [corrected].
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 N-acetylglucosamine, 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.
authors.affiliation: Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Oeiras, Portugal.
authors.forename: Laura
authors.initials: L
authors.lastname: Paixão
authors.affiliation: Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Oeiras, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Oliveira
authors.affiliation: Centre for Intelligent Systems, LAETA, IDMEC, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal.
authors.forename: André
authors.initials: A
authors.lastname: Veríssimo
authors.affiliation: Centre for Intelligent Systems, LAETA, IDMEC, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Susana
authors.initials: S
authors.lastname: Vinga
authors.affiliation: Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Oeiras, Portugal.
authors.forename: Eva C
authors.initials: EC
authors.lastname: Lourenço
authors.affiliation: Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Oeiras, Portugal.
authors.forename: M Rita
authors.initials: MR
authors.lastname: Ventura
authors.affiliation: Molecular Genetics Group, Groningen Biomolecular Sciences and Biotechnology Institute, Centre for Synthetic Biology, University of Groningen, Groningen, The Netherlands.
authors.forename: Morten
authors.initials: M
authors.lastname: Kjos
authors.affiliation: Molecular Genetics Group, Groningen Biomolecular Sciences and Biotechnology Institute, Centre for Synthetic Biology, University of Groningen, Groningen, The Netherlands.
authors.forename: Jan-Willem
authors.initials: JW
authors.lastname: Veening
authors.affiliation: Department of Infection, Immunity & Inflammation, University of Leicester, Leicester, United Kingdom.
authors.forename: Vitor E
authors.initials: VE
authors.lastname: Fernandes
authors.affiliation: Department of Infection, Immunity & Inflammation, University of Leicester, Leicester, United Kingdom.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Andrew
authors.affiliation: Department of Infection, Immunity & Inflammation, University of Leicester, Leicester, United Kingdom.
authors.forename: Hasan
authors.initials: H
authors.lastname: Yesilkaya
authors.affiliation: Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Oeiras, Portugal.
authors.forename: Ana Rute
authors.initials: AR
authors.lastname: Neves
mesh_terms: D005690:Galactose / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D009077:Mucins / Q000378:metabolism; D011134:Polysaccharides / Q000378:metabolism*; D013290:Streptococcal Infections / Q000378:metabolism*; D013296:Streptococcus pneumoniae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D014774:Virulence
chemical_list: D009077:Mucins; D011134:Polysaccharides; D005690:Galactose
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