Sp_0916 Is An Arginine Decarboxylase That Catalyzes The Synthesis Of Agmatine, Which Is Critical For Capsule Biosynthesis Instreptococcus Pneumoniae

The global burden of invasive pneumococcal diseases, including pneumonia and sepsis, caused byStreptococcus pneumoniae, a Gram-positive bacterial pathogen, remains a major global health risk. The success of pneumococcus as a pathogen can be attributed to its ability to regulate the synthesis of capsular polysaccharide (CPS) during invasive disease. We previously reported that deletion of a putative lysine decarboxylase (LDC; Delta SP_0916) in pneumococcal serotype 4 (TIGR4) results in reduced CPS. SP_0916 locus is annotated as either an arginine or a LDC in pneumococcal genomes. In this study, by biochemical characterization of the recombinant SP_0916, we determined the substrate specificity of SP_0916 and show that it is an arginine decarboxylase (speA/ADC). We also show that deletion of the polyamine transporter (potABCD) predicted to import putrescine and spermidine results in reduced CPS, while deletion of spermidine synthase (speE) for the conversion of putrescine to spermidine had no impact on the capsule. Targeted metabolomics identified a correlation between reduced levels of agmatine and loss of capsule in Delta speAand Delta potABCD, while agmatine levels were comparable between the encapsulated TIGR4 and Delta speE. Exogenous supplementation of agmatine restored CPS in both Delta potABCDand Delta speA. These results demonstrate that agmatine is critical for regulating the CPS, a predominant virulence factor in pneumococci.