革兰氏阴性菌锌摄取机制及抵抗宿主营养免疫的策略

The Mechanism of Zinc Uptake in Gram-negative Bacteria and Strategies for Resisting Host Nutrition Immunity

锌是一种重要的金属元素,不仅充当许多蛋白质和酶的辅因子,还广泛参与糖类、脂质等的代谢过程。锌通常以二价离子的形式存在,在自然界主要分布在植物、土壤和水中,而在生物体内则是分散于肌肉和骨等组织中。对于大多数革兰氏阴性菌而言,锌离子也是其生长过程中必不可少的营养物质。正常情况下,细菌通过ZnuABC和ZIP锌转运系统从宿主体内夺取锌离子,用于体内蛋白质和酶的合成。当过多的锌离子被摄入时,细菌为了避免锌毒性则会启动特定的锌转录调节蛋白,以维持体内外的锌平衡。另一方面,当宿主察觉体内的锌离子被夺取,便会迅速采取锌限制性营养免疫等措施来制止锌离子的进一步流失。为了抵抗宿主的营养免疫,细菌进化出了相应的抵抗策略。较为典型的例子有鲍曼不动杆菌(Acinetobacter baumannii)的锌金属伴侣ZigA,其可在低锌环境中帮助细菌转运锌离子。本文将介绍革兰氏阴性菌锌摄取机制和抵抗宿主营养免疫的典型策略,为控制细菌感染途径和开发相关免疫疫苗等方面提供理论依据。

Zinc is an important metal element for most organisms.It not only acts as a cofactor for many proteins and enzymes,but also is widely involved in the metabolism of sugars and lipids.Zinc is usually present in the form of divalent ions,which are mainly distributed in plants,soil and water in the environment,and muscles,bones or other tissues in the animal.For most of Gram-negative bacteria,zinc ions are also essential nutrients for the growth.Usually,bacteria take zinc ions from the host through the ZnuABC and ZIP zinc transport systems.However,excess zinc ions are toxic,the bacteria use a specific zinc transcriptional regulatory protein to avoid zinc toxicity to maintain zinc balance.On the other side,when the host finds that the zinc ions in the body have been seized,it will quickly take measures such as zinc-restricted nutrient immunity to prevent further loss.Therefore,in order to resist the host’s nutrient immunity,the bacteria have evolved corresponding resistance strategies.For example,the zinc metal chaperone ZigA of Acinetobacter baumannii,which helps bacteria transport zinc ions in a low-zinc environment.This review will describe the mechanism of zinc uptake in Gram-negative bacteria and the strategies against host nutrient immunity.It will provide the theoretical foundation for controlling bacterial infection pathways and developing the vaccines.