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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

Pneumococcal strains defective in galactose catabolic pathways are less able to colonise nasopharynx.Mice were infected with approximately 1 X 105 CFU pneumococci. At predetermined times, five mice were culled, and CFU mg-1 of bacteria were determined by serial dilutions of nasopharyngeal homogenates. Each column represents the mean of data from five mice. Error bars show the standard error of the mean. Symbols: * p<0.05; ** p<0.01, **** p<0.0001.
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pone.0121042.g008: Pneumococcal strains defective in galactose catabolic pathways are less able to colonise nasopharynx.Mice were infected with approximately 1 X 105 CFU pneumococci. At predetermined times, five mice were culled, and CFU mg-1 of bacteria were determined by serial dilutions of nasopharyngeal homogenates. Each column represents the mean of data from five mice. Error bars show the standard error of the mean. Symbols: * p<0.05; ** p<0.01, **** p<0.0001.

Mentions: In the colonisation model, the counts for all the pneumococcal strains were determined in nasopharyngeal tissue at the time of infection, and at 3 and 7 days after infection (Fig 8). The results show that at 3 and 7 days post-infection the numbers of D39ΔgalK (log10 1.75±0.14 and log10 1.80±0.17 n = 5), D39ΔlacD (log10 1.72±0.2 and log10 1.87±0.24, n = 5), and D39ΔlacDΔgalK (log10 1.08±0.33 and log10 0.89±0.25, n = 5) were significantly lower than the counts of wild type (log10 2.82±0.02; and log10 2.77±0.08, n = 5, for days 3 and 7, respectively) (p<0.01 for D39ΔgalK, p<0.0001 for D39ΔlacDΔgalK, and p<0.01 and p<0.05 for D39ΔlacD for 3 and 7 days post-infection, respectively). Similar to the bronchopneumonia model, in the colonisation model no phenotypic differences were observed between the wild type and D39ΔgalKcomp, D39 ΔlacDcomp (Fig 8) (p>0.05), and the wild type and D39 ΔmanA and D39 ΔnagA (data not shown).


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)

Pneumococcal strains defective in galactose catabolic pathways are less able to colonise nasopharynx.Mice were infected with approximately 1 X 105 CFU pneumococci. At predetermined times, five mice were culled, and CFU mg-1 of bacteria were determined by serial dilutions of nasopharyngeal homogenates. Each column represents the mean of data from five mice. Error bars show the standard error of the mean. Symbols: * p<0.05; ** p<0.01, **** p<0.0001.
© Copyright Policy
Related In: Results  -  Collection

License
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getmorefigures.php?uid=PMC4380338&req=5

pone.0121042.g008: Pneumococcal strains defective in galactose catabolic pathways are less able to colonise nasopharynx.Mice were infected with approximately 1 X 105 CFU pneumococci. At predetermined times, five mice were culled, and CFU mg-1 of bacteria were determined by serial dilutions of nasopharyngeal homogenates. Each column represents the mean of data from five mice. Error bars show the standard error of the mean. Symbols: * p<0.05; ** p<0.01, **** p<0.0001.
Mentions: In the colonisation model, the counts for all the pneumococcal strains were determined in nasopharyngeal tissue at the time of infection, and at 3 and 7 days after infection (Fig 8). The results show that at 3 and 7 days post-infection the numbers of D39ΔgalK (log10 1.75±0.14 and log10 1.80±0.17 n = 5), D39ΔlacD (log10 1.72±0.2 and log10 1.87±0.24, n = 5), and D39ΔlacDΔgalK (log10 1.08±0.33 and log10 0.89±0.25, n = 5) were significantly lower than the counts of wild type (log10 2.82±0.02; and log10 2.77±0.08, n = 5, for days 3 and 7, respectively) (p<0.01 for D39ΔgalK, p<0.0001 for D39ΔlacDΔgalK, and p<0.01 and p<0.05 for D39ΔlacD for 3 and 7 days post-infection, respectively). Similar to the bronchopneumonia model, in the colonisation model no phenotypic differences were observed between the wild type and D39ΔgalKcomp, D39 ΔlacDcomp (Fig 8) (p>0.05), and the wild type and D39 ΔmanA and D39 ΔnagA (data not shown).

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