基于细菌代谢探讨精氨酸在金黄色葡萄球菌感染巨噬细胞进程中的作用

Role of arginine in the progression of Staphylococcus aureus infection in macrophages through the lens of bacterial metabolism

摘要:

金黄色葡萄球菌(Staphylococcus aureus)作为常见的医院获得性感染病原菌，长期严重威胁公共卫生安全，造成了巨大的社会经济负担。精氨酸作为条件必需氨基酸，在S. aureus感染致病与宿主免疫应答中发挥着双重调控作用：一方面，精氨酸的合成与分解参与S. aureus生物被膜形成和耐药性建立；另一方面，精氨酸代谢通过影响巨噬细胞极化、免疫调节、代谢重编程以及信号转导等途径，在宿主抗感染免疫、组织修复和伤口愈合中发挥重要作用。鉴于精氨酸的合成与分解是S. aureus-巨噬细胞互作的关键调控枢纽，其代谢平衡影响感染与抗感染的进程和转归。因此，通过靶向调控精氨酸代谢来控制S. aureus感染是具有重要转化医学价值的新策略。本文以精氨酸代谢为核心，分别阐述S. aureus和巨噬细胞如何通过竞争与利用精氨酸来发挥各自的生物学功能，并深入剖析精氨酸水平变化在S. aureus-巨噬细胞互作中的关键作用，探讨调节精氨酸代谢这一潜在抗菌策略可进一步开展的研究方向与可能面临的挑战。

Abstract:

Staphylococcus aureus, a common foodborne pathogen causing hospital-acquired infection, poses a grave threat to public health and safety, resulting in a substantial economic burden on the society. As a conditionally essential amino acid, arginine exhibits a dual role in the infection of S. aureus and the immune response of the host. On the one hand, arginine synthesis and catabolism are involved in pathogenic processes such as the biofilm formation and antibiotic resistance of S. aureus. On the other hand, arginine metabolites play an important role in anti-infective immunity, tissue repair, and wound healing through the modulation of macrophage polarization, immune modulation, metabolic reprogramming, and signaling. Recent studies suggest that arginine metabolism constitutes a regulatory hub for S. aureus-macrophage interactions, and its metabolic balance affects the progression and regression of infection and anti-infection. Consequently, targeting the arginine metabolic pathway to impede S. aureus infection by regulating host-pathogen metabolic interactions has emerged as a novel anti-S. aureus therapeutic strategy with significant translational medical relevance. In this review, we focus on the metabolic utilization of arginine to describe how S. aureus and macrophages exert their respective biological functions by competing for the utilization of arginine. In addition, we summarize the changes of arginine levels in macrophages during S. aureus infection to explore the feasible research directions and challenges of regulating arginine metabolism as a potential antimicrobial strategy in the future.