School of Pharmacy, Sungkyunkwan University, Suwon, 16419, South Korea.
Arch Pharm Res. 2017 Aug;40(8):921-932. doi: 10.1007/s12272-017-0931-0. Epub 2017 Jul 22.
Streptococcus pneumoniae (pneumococcus) is responsible for significant morbidity and mortality worldwide. It causes a variety of life-threatening infections such as pneumonia, bacteremia, and meningitis. In bacterial physiology, the metabolic pathway of branched-chain amino acids (BCAAs) plays an important role in virulence. Nonetheless, the function of IlvC, one of the enzymes involved in the biosynthesis of BCAAs, in S. pneumoniae remains unclear. Here, we demonstrated that downregulation of BCAA biosynthesis by ilvC ablation can diminish BCAA concentration and expression of pneumolysin (Ply) and LytA, and subsequently attenuate virulence. Infection with an ilvC mutant showed significantly reduced mortality and colonization in comparison with strain D39 (serotype 2, wild type), suggesting that ilvC can potentiate S. pneumoniae virulence due to adequate BCAA synthesis. Taken together, these results suggest that the function of ilvC in BCAA synthesis is essential for virulence factor and could play an important role in the pathogenesis of respiratory infections.
肺炎链球菌（肺炎球菌）在全球范围内导致了大量的发病率和死亡率。它会引起各种危及生命的感染，如肺炎、菌血症和脑膜炎。在细菌生理学中，支链氨基酸（BCAAs）的代谢途径在毒力中起着重要作用。然而，参与 BCAAs 生物合成的酶之一 IlvC 在肺炎链球菌中的功能仍不清楚。在这里，我们证明了通过 ilvC 缺失来下调 BCAAs 的生物合成，可以降低 BCAA 浓度以及肺炎链球菌溶血素（Ply）和 LytA 的表达，从而减弱其毒力。与菌株 D39（血清型 2，野生型）相比，感染 ilvC 突变体的小鼠的死亡率和定植率明显降低，这表明由于足够的 BCAA 合成，ilvC 可以增强肺炎链球菌的毒力。总之，这些结果表明，ilvC 在 BCAAs 合成中的功能对于毒力因子至关重要，并且可能在呼吸道感染的发病机制中发挥重要作用。
