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. 2019 Aug 29;10:1996. doi: 10.3389/fmicb.2019.01996

FIGURE 5.

FIGURE 5

Intersection between polyamine biosynthesis, carbohydrate metabolism, and the capsule in pneumococci. Interconnected metabolic pathways in a putative lysine decarboxylase synthesis deficient strain of S. pneumoniae TIGR4 (ΔcadA) analyzed by RNA-Seq and metabolomics identified specific molecular mechanisms that could result in reduced intracellular levels of the constituents of the serotype four capsule and PG repeat structures. Enzymatic reactions are shown as black arrows and multi-step reactions are represented by a broken arrow. Changes in gene (italicized) and metabolite levels in ΔcadA relative to the wild-type strain are shown (red represents decrease and blue represents increase). Deletion of cadA results in reduced expression of genes encoding biosynthesis pathways of polyamines such as putrescine, spermidine, and spermine and precursor amino acid lysine. Accumulation of arginosuccinate, an intermediate for the biosynthesis of arginine supports the notion of overall reduction in polyamine synthesis in ΔcadA. Impaired polyamine synthesis renders pneumococci incapable of UDP-Glu to UDP-Gal interconversion, i.e., Leloir pathway (gray square), that could reduce the carbon flux through glycolysis (yellow rectangle). Despite increased carbon flux toward G3P, a glycolytic intermediate, through tagatose metabolism, changes in the levels of metabolites of glycolysis indicate reduced carbon flux. RNA-Seq data indicated that G3P is routed through the PPP (green square), and enhanced PPP activity will result in increased nucleotide synthesis. Changes in amino and nucleotide sugar metabolism (blue square) will result in reduced intracellular levels of UDP-GlcNAc, a precursor for three N-acetylated sugars in the serotype 4 capsule repeat unit (precursor nucleotide sugars shown in the open oval). Impaired Leloir pathway and UDP-GlcNAc synthesis will limit the availability of CPS precursors. Changes in metabolism in ΔcadA, such as reduced glycolytic activity, altered UDP-GlcNAc metabolism and lysine synthesis impacts the assembly of the PG repeat unit (open rectangle) disaccharide and pentapeptide (light green rectangle). Polymerization of PG repeat units generates the cell wall which provides attachment for the capsule.