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Host glycan sugar-specific pathways in Streptococcus pneumoniae: galactose as a key sugar in colonisation and infection [corrected].

Paixão L, Oliveira J, Veríssimo A, Vinga S, Lourenço EC, Ventura MR, Kjos M, Veening JW, Fernandes VE, Andrew PW, Yesilkaya H, Neves AR - PLoS ONE (2015)

Bottom Line: Therefore, it is reasonable to hypothesise that the pneumococcus would rely on these glycan-derived sugars to grow.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.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.

View Article: PubMed Central - PubMed

Affiliation: Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Oeiras, Portugal.

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.

No MeSH data available.


Related in: MedlinePlus

Schematic representation of the proposed pathways for the dissimilation of monosaccharides originating from deglycosylation of host glycans in S. pneumoniae D39.Pathways were reconstructed resorting to metabolic databases (MetaCyc and KEGG), genome annotations at NCBI and literature. Genes and intermediates involved in the galactose (Gal), mannose (Man), N-acetylneuraminic acid (NeuNAc), N-acetylgalactosamine (GalNAc), N-acetylglucosamine (GlcNAc) and fucose (Fuc) catabolism are shown. Initial steps of glycolysis are depicted. galM, aldolase 1-epimerase; galK, galactokinase; galT-1, galT-2, galactose 1-phosphate uridylyltransferase; galE-1, galE-2, UDP-glucose 4-epimerase; pgm, phosphoglucomutase/phosphomannomutase family protein; lacA, galactose 6-phosphate isomerase subunit LacA; lacB, galactose 6-phosphate isomerase subunit LacB; lacC, tagatose 6-phosphate kinase; lacD, tagatose 1,6-diphosphate aldolase; manA, mannose 6-phosphate isomerase; SPD_1489, SPD_1163, N-acetylneuraminate lyase; SPD_1488, ROK family protein, nanE-1, nanE-2, N-acetylmannosamine 6-phosphate 2-epimerase; nagA, N-acetylglucosamine 6-phosphate deacetylase; nagB, glucosamine 6-phosphate isomerase; fucI, L-fucose isomerase; fucK, L-fuculose kinase; fucA, L-fuculose phosphate aldolase. α-Gal, α-galactose; α-Gal1P, α-galactose 1-phosphate; α-G1P, α-glucose 1-phosphate; UDP-Glc, UDP-glucose; UDP-Gal, UDP-galactose; Gal6P, galactose 6-phosphate; T6P, tagatose 6-phosphate; TBP, tagatose 1,6-diphosphate; Man6P, mannose 6-phosphate; ManNAc, N-acetylmannosamine; ManNAc6P, N-acetylmannosamine 6-phosphate; GlcNAc6P, N-acetylglucosamine 6-phosphate; GlcN6P, glucosamine 6-phosphate; Fucl, fuculose; Fucl1P, fuculose 1-phosphate; GalNAc6P, N-acetylgalactosamine 6-phosphate; GalN6P, galactosamine 6-phosphate. The upper glycolytic intermediates and gene annotations are as follows: G6P, glucose 6-phosphate; F6P, fructose 6-phosphate; FBP, fructose 1,6-biphosphate; GAP, glyceraldehyde 3-phosphate; DHAP, dihydroxyacetone phosphate. gki, glucokinase; pgi, glucose 6-phosphate isomerase; pfkA, 6-phosphofructokinase; fba, fructose-biphosphate aldolase; tpiA, triosephosphate isomerase. The lower glycolytic pathway is represented by a dashed arrow. Pathways or steps present in other organisms but uncertain in D39 are represented in grey. Vertical arrows near the gene name indicate the upregulation during growth on mucin as compared to Glc, in S. pneumoniae D39.
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pone.0121042.g001: Schematic representation of the proposed pathways for the dissimilation of monosaccharides originating from deglycosylation of host glycans in S. pneumoniae D39.Pathways were reconstructed resorting to metabolic databases (MetaCyc and KEGG), genome annotations at NCBI and literature. Genes and intermediates involved in the galactose (Gal), mannose (Man), N-acetylneuraminic acid (NeuNAc), N-acetylgalactosamine (GalNAc), N-acetylglucosamine (GlcNAc) and fucose (Fuc) catabolism are shown. Initial steps of glycolysis are depicted. galM, aldolase 1-epimerase; galK, galactokinase; galT-1, galT-2, galactose 1-phosphate uridylyltransferase; galE-1, galE-2, UDP-glucose 4-epimerase; pgm, phosphoglucomutase/phosphomannomutase family protein; lacA, galactose 6-phosphate isomerase subunit LacA; lacB, galactose 6-phosphate isomerase subunit LacB; lacC, tagatose 6-phosphate kinase; lacD, tagatose 1,6-diphosphate aldolase; manA, mannose 6-phosphate isomerase; SPD_1489, SPD_1163, N-acetylneuraminate lyase; SPD_1488, ROK family protein, nanE-1, nanE-2, N-acetylmannosamine 6-phosphate 2-epimerase; nagA, N-acetylglucosamine 6-phosphate deacetylase; nagB, glucosamine 6-phosphate isomerase; fucI, L-fucose isomerase; fucK, L-fuculose kinase; fucA, L-fuculose phosphate aldolase. α-Gal, α-galactose; α-Gal1P, α-galactose 1-phosphate; α-G1P, α-glucose 1-phosphate; UDP-Glc, UDP-glucose; UDP-Gal, UDP-galactose; Gal6P, galactose 6-phosphate; T6P, tagatose 6-phosphate; TBP, tagatose 1,6-diphosphate; Man6P, mannose 6-phosphate; ManNAc, N-acetylmannosamine; ManNAc6P, N-acetylmannosamine 6-phosphate; GlcNAc6P, N-acetylglucosamine 6-phosphate; GlcN6P, glucosamine 6-phosphate; Fucl, fuculose; Fucl1P, fuculose 1-phosphate; GalNAc6P, N-acetylgalactosamine 6-phosphate; GalN6P, galactosamine 6-phosphate. The upper glycolytic intermediates and gene annotations are as follows: G6P, glucose 6-phosphate; F6P, fructose 6-phosphate; FBP, fructose 1,6-biphosphate; GAP, glyceraldehyde 3-phosphate; DHAP, dihydroxyacetone phosphate. gki, glucokinase; pgi, glucose 6-phosphate isomerase; pfkA, 6-phosphofructokinase; fba, fructose-biphosphate aldolase; tpiA, triosephosphate isomerase. The lower glycolytic pathway is represented by a dashed arrow. Pathways or steps present in other organisms but uncertain in D39 are represented in grey. Vertical arrows near the gene name indicate the upregulation during growth on mucin as compared to Glc, in S. pneumoniae D39.

Mentions: Host glycans are rich in the carbohydrate monomers Gal, GalNAc, GlcNAc, NeuNAc, mannose (Man) and Fuc. We set out to uncover the genomic potential of S. pneumoniae D39 for utilization of these sugars and amino sugars by performing pathway reconstruction using data from the literature and deposited in metabolic databases (MetaCyc and Kegg), as well as by protein homology (BlastP) to functionally characterized enzymes (Fig 1 and S4 Table). In general, our systematic analysis confirmed genome annotations, and a schematic representation of the inferred sugar catabolic pathways is depicted in Fig 1. A more detailed description is provided as supplemental material (S4 Table and S2 Text).


Host glycan sugar-specific pathways in Streptococcus pneumoniae: galactose as a key sugar in colonisation and infection [corrected].

Paixão L, Oliveira J, Veríssimo A, Vinga S, Lourenço EC, Ventura MR, Kjos M, Veening JW, Fernandes VE, Andrew PW, Yesilkaya H, Neves AR - PLoS ONE (2015)

Schematic representation of the proposed pathways for the dissimilation of monosaccharides originating from deglycosylation of host glycans in S. pneumoniae D39.Pathways were reconstructed resorting to metabolic databases (MetaCyc and KEGG), genome annotations at NCBI and literature. Genes and intermediates involved in the galactose (Gal), mannose (Man), N-acetylneuraminic acid (NeuNAc), N-acetylgalactosamine (GalNAc), N-acetylglucosamine (GlcNAc) and fucose (Fuc) catabolism are shown. Initial steps of glycolysis are depicted. galM, aldolase 1-epimerase; galK, galactokinase; galT-1, galT-2, galactose 1-phosphate uridylyltransferase; galE-1, galE-2, UDP-glucose 4-epimerase; pgm, phosphoglucomutase/phosphomannomutase family protein; lacA, galactose 6-phosphate isomerase subunit LacA; lacB, galactose 6-phosphate isomerase subunit LacB; lacC, tagatose 6-phosphate kinase; lacD, tagatose 1,6-diphosphate aldolase; manA, mannose 6-phosphate isomerase; SPD_1489, SPD_1163, N-acetylneuraminate lyase; SPD_1488, ROK family protein, nanE-1, nanE-2, N-acetylmannosamine 6-phosphate 2-epimerase; nagA, N-acetylglucosamine 6-phosphate deacetylase; nagB, glucosamine 6-phosphate isomerase; fucI, L-fucose isomerase; fucK, L-fuculose kinase; fucA, L-fuculose phosphate aldolase. α-Gal, α-galactose; α-Gal1P, α-galactose 1-phosphate; α-G1P, α-glucose 1-phosphate; UDP-Glc, UDP-glucose; UDP-Gal, UDP-galactose; Gal6P, galactose 6-phosphate; T6P, tagatose 6-phosphate; TBP, tagatose 1,6-diphosphate; Man6P, mannose 6-phosphate; ManNAc, N-acetylmannosamine; ManNAc6P, N-acetylmannosamine 6-phosphate; GlcNAc6P, N-acetylglucosamine 6-phosphate; GlcN6P, glucosamine 6-phosphate; Fucl, fuculose; Fucl1P, fuculose 1-phosphate; GalNAc6P, N-acetylgalactosamine 6-phosphate; GalN6P, galactosamine 6-phosphate. The upper glycolytic intermediates and gene annotations are as follows: G6P, glucose 6-phosphate; F6P, fructose 6-phosphate; FBP, fructose 1,6-biphosphate; GAP, glyceraldehyde 3-phosphate; DHAP, dihydroxyacetone phosphate. gki, glucokinase; pgi, glucose 6-phosphate isomerase; pfkA, 6-phosphofructokinase; fba, fructose-biphosphate aldolase; tpiA, triosephosphate isomerase. The lower glycolytic pathway is represented by a dashed arrow. Pathways or steps present in other organisms but uncertain in D39 are represented in grey. Vertical arrows near the gene name indicate the upregulation during growth on mucin as compared to Glc, in S. pneumoniae D39.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4380338&req=5

pone.0121042.g001: Schematic representation of the proposed pathways for the dissimilation of monosaccharides originating from deglycosylation of host glycans in S. pneumoniae D39.Pathways were reconstructed resorting to metabolic databases (MetaCyc and KEGG), genome annotations at NCBI and literature. Genes and intermediates involved in the galactose (Gal), mannose (Man), N-acetylneuraminic acid (NeuNAc), N-acetylgalactosamine (GalNAc), N-acetylglucosamine (GlcNAc) and fucose (Fuc) catabolism are shown. Initial steps of glycolysis are depicted. galM, aldolase 1-epimerase; galK, galactokinase; galT-1, galT-2, galactose 1-phosphate uridylyltransferase; galE-1, galE-2, UDP-glucose 4-epimerase; pgm, phosphoglucomutase/phosphomannomutase family protein; lacA, galactose 6-phosphate isomerase subunit LacA; lacB, galactose 6-phosphate isomerase subunit LacB; lacC, tagatose 6-phosphate kinase; lacD, tagatose 1,6-diphosphate aldolase; manA, mannose 6-phosphate isomerase; SPD_1489, SPD_1163, N-acetylneuraminate lyase; SPD_1488, ROK family protein, nanE-1, nanE-2, N-acetylmannosamine 6-phosphate 2-epimerase; nagA, N-acetylglucosamine 6-phosphate deacetylase; nagB, glucosamine 6-phosphate isomerase; fucI, L-fucose isomerase; fucK, L-fuculose kinase; fucA, L-fuculose phosphate aldolase. α-Gal, α-galactose; α-Gal1P, α-galactose 1-phosphate; α-G1P, α-glucose 1-phosphate; UDP-Glc, UDP-glucose; UDP-Gal, UDP-galactose; Gal6P, galactose 6-phosphate; T6P, tagatose 6-phosphate; TBP, tagatose 1,6-diphosphate; Man6P, mannose 6-phosphate; ManNAc, N-acetylmannosamine; ManNAc6P, N-acetylmannosamine 6-phosphate; GlcNAc6P, N-acetylglucosamine 6-phosphate; GlcN6P, glucosamine 6-phosphate; Fucl, fuculose; Fucl1P, fuculose 1-phosphate; GalNAc6P, N-acetylgalactosamine 6-phosphate; GalN6P, galactosamine 6-phosphate. The upper glycolytic intermediates and gene annotations are as follows: G6P, glucose 6-phosphate; F6P, fructose 6-phosphate; FBP, fructose 1,6-biphosphate; GAP, glyceraldehyde 3-phosphate; DHAP, dihydroxyacetone phosphate. gki, glucokinase; pgi, glucose 6-phosphate isomerase; pfkA, 6-phosphofructokinase; fba, fructose-biphosphate aldolase; tpiA, triosephosphate isomerase. The lower glycolytic pathway is represented by a dashed arrow. Pathways or steps present in other organisms but uncertain in D39 are represented in grey. Vertical arrows near the gene name indicate the upregulation during growth on mucin as compared to Glc, in S. pneumoniae D39.
Mentions: Host glycans are rich in the carbohydrate monomers Gal, GalNAc, GlcNAc, NeuNAc, mannose (Man) and Fuc. We set out to uncover the genomic potential of S. pneumoniae D39 for utilization of these sugars and amino sugars by performing pathway reconstruction using data from the literature and deposited in metabolic databases (MetaCyc and Kegg), as well as by protein homology (BlastP) to functionally characterized enzymes (Fig 1 and S4 Table). In general, our systematic analysis confirmed genome annotations, and a schematic representation of the inferred sugar catabolic pathways is depicted in Fig 1. A more detailed description is provided as supplemental material (S4 Table and S2 Text).

Bottom Line: Therefore, it is reasonable to hypothesise that the pneumococcus would rely on these glycan-derived sugars to grow.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.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.

View Article: PubMed Central - PubMed

Affiliation: Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Oeiras, Portugal.

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.

No MeSH data available.


Related in: MedlinePlus