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Cheng, Zhi-Xue; Guo, Chang; Chen, Zhuang-Gui; Yang, Tian-Ci; Zhang, Jian-Ying; Wang, Jie; Zhu, Jia-Xin; Li, Dan; Zhang, Tian-Tuo; Li, Hui; Peng, Bo; Peng, Xuan-Xian
Nature communications, 07/2019, Volume: 10, Issue: 1Journal Article
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.
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