Center for Proteomics and Metabolomics, State Key Laboratory of Bio-Control, School of Life Sciences, Sun Yat-sen University, University City, Guangzhou, 510006, People's Republic of China.
Laboratory for Marine Biology and Biotechnology, Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266071, China.
Nat Commun. 2019 Jul 25;10(1):3325. doi: 10.1038/s41467-019-11129-5.
Serum resistance is a poorly understood but common trait of some difficult-to-treat pathogenic strains of bacteria. Here, we report that glycine, serine and threonine catabolic pathway is down-regulated in serum-resistant Escherichia coli, whereas exogenous glycine reverts the serum resistance and effectively potentiates serum to eliminate clinically-relevant bacterial pathogens in vitro and in vivo. We find that exogenous glycine increases the formation of membrane attack complex on bacterial membrane through two previously unrecognized regulations: 1) glycine negatively and positively regulates metabolic flux to purine biosynthesis and Krebs cycle, respectively. 2) α-Ketoglutarate inhibits adenosine triphosphate synthase, which in together promote the formation of cAMP/CRP regulon to increase the expression of complement-binding proteins HtrE, NfrA, and YhcD. The results could lead to effective strategies for managing the infection with serum-resistant bacteria, an especially valuable approach for treating individuals with weak acquired immunity but a normal complement system.
血清抗性是一些难以治疗的病原菌菌株的一个尚未被充分理解但却很常见的特征。在这里，我们报告称，在血清抗性大肠杆菌中，甘氨酸、丝氨酸和苏氨酸分解代谢途径被下调，而外源性甘氨酸则恢复了血清抗性，并有效地增强了血清在体外和体内消除临床相关细菌病原体的能力。我们发现，外源性甘氨酸通过两种以前未被认识到的调节方式增加了细菌膜上膜攻击复合物的形成：1）甘氨酸分别负向和正向调节嘌呤生物合成和克雷布斯循环的代谢通量。2）α-酮戊二酸抑制三磷酸腺苷合酶，共同促进 cAMP/CRE 调控子的形成，增加补体结合蛋白 HtrE、NfrA 和 YhcD 的表达。这些结果可能为管理血清抗性细菌感染提供有效的策略，对于治疗具有弱获得性免疫但正常补体系统的个体尤其有价值。
