Figure 4.

Mechanisms for reduced capsule synthesis in lysine decarboxylase deficient pneumococci. Deletion of lysine decarboxylase in pneumococci results in reduced capsule compared to wild type TIGR4 strain. Reduced capsule synthesis could be due to the reduced expression (shown in red) of capsular polysaccharide biosynthesis gene cps4A, the first gene in the cps locus in S. pneumoniae TIGR4 (A). The first four genes from the cps locus adjacent to the gene dexB that are conserved in all pneumococcal serotypes are shown. Our proteomics data indicates a shift in central metabolism (B) from glycolysis (yellow box) to the non-oxidative branch of pentose phosphate pathway (green box), due to increased expression (shown in blue) of transketolase (Tkt,). Reactions that involve multiple steps are represented by a broken line. Reduced expression of GlmU involved in the synthesis and increased expression of NagB involved in the degradation of UDP-GlcNAc could result in reduced concentration of UDP-GlcNAc. UDP-GlcNAc is a precursor for UDP-ManNAc, an acetylated sugar that is the constituent of the 4-sugar repeat unit of capsular polysaccharide in capsular serotype 4 (open oval). The net effect of these changes in pneumococcal gene and protein expression could result in the observed reduction in capsule biosynthesis in ΔcadA.