Ayoola Moses B, Nakamya Mary F, Shack Leslie A, Park Seongbin, Lim Juhyeon, Lee Jung Hwa, Ross Matthew K, Eoh Hyungjin, Nanduri Bindu
Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Starkville, MS, United States.
Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, CA, United States.
Front Microbiol. 2020 Sep 18;11:578533. doi: 10.3389/fmicb.2020.578533. eCollection 2020.
The global burden of invasive pneumococcal diseases, including pneumonia and sepsis, caused by , 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 (/ADC). We also show that deletion of the polyamine transporter () predicted to import putrescine and spermidine results in reduced CPS, while deletion of spermidine synthase () 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 Δ and Δ, while agmatine levels were comparable between the encapsulated TIGR4 and Δ. Exogenous supplementation of agmatine restored CPS in both Δ and Δ. These results demonstrate that agmatine is critical for regulating the CPS, a predominant virulence factor in pneumococci.
由革兰氏阳性细菌病原体肺炎链球菌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仍然是一个重大的全球健康风险。肺炎球菌作为病原体的成功可归因于其在侵袭性疾病期间调节荚膜多糖（CPS）合成的能力。我们之前报道过，肺炎球菌血清型4（TIGR4）中假定的赖氨酸脱羧酶（LDC；ΔSP_0916）缺失会导致CPS减少。在肺炎球菌基因组中，SP_0916基因座被注释为精氨酸脱羧酶或赖氨酸脱羧酶。在本研究中，通过对重组SP_0916进行生化特性分析，我们确定了SP_0916的底物特异性，并表明它是一种精氨酸脱羧酶（/ADC）。我们还表明，预测可导入腐胺和亚精胺的多胺转运体（）缺失会导致CPS减少，而将腐胺转化为亚精胺的亚精胺合酶（）缺失对荚膜没有影响。靶向代谢组学确定了在Δ和Δ中，胍丁胺水平降低与荚膜丧失之间存在相关性，而在有荚膜的TIGR4和Δ之间，胍丁胺水平相当。外源补充胍丁胺可恢复Δ和Δ中的CPS。这些结果表明，胍丁胺对于调节CPS至关重要，CPS是肺炎球菌中的一种主要毒力因子。
