The global burden of invasive pneumococcal diseases, including pneumonia and sepsis, caused by Streptococcus 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; ΔSP_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 ΔspeA and ΔpotABCD, while agmatine levels were comparable between the encapsulated TIGR4 and ΔspeE. Exogenous supplementation of agmatine restored CPS in both ΔpotABCD and ΔspeA. These results demonstrate that agmatine is critical for regulating the CPS, a predominant virulence factor in pneumococci.

由下列因素引起的包括肺炎和败血症在内的侵袭性肺炎球菌疾病的全球负担 肺炎链球菌革兰氏阳性细菌病原体仍然是主要的全球健康风险。肺炎球菌作为病原体的成功可归因于其在浸润性疾病期间调节荚膜多糖（CPS）合成的能力。我们先前曾报道，肺炎球菌血清型4（TIGR4）中假定的赖氨酸脱羧酶（LDC;ΔSP_0916）的缺失导致CPS降低。SP_0916基因座在肺炎球菌基因组中标注为精氨酸或LDC。在这项研究中，通过重组SP_0916的生化表征，我们确定了SP_0916的底物特异性，并证明它是精氨酸脱羧酶（特殊规格/ ADC）。我们还显示了多胺转运蛋白的缺失（potABCD）预计会进口腐胺和亚精胺导致CPS降低，而亚精胺合酶（速度），以将腐胺转化为亚精胺对胶囊没有影响。靶向代谢组学确定了胍丁胺水平降低与Δ胶囊丢失之间的相关性特殊规格 和ΔpotABCD，而包封的TIGR4和Δ之间的胍丁胺水平相当速度。外源补充胍丁胺可恢复CPS的两个ΔpotABCD 和Δ特殊规格。这些结果表明，胍丁胺对于调节CPS（肺炎球菌中的主要毒力因子）至关重要。