细菌VI型分泌系统转运金属离子的功能及机制研究

Study on the function of bacterial type VI secretion systems (T6SSs) and their effector proteins is currently a new hotspot in the field of microbiology. Based on our recently discovery of a novel type of T6SS effectors, the ion-binding effectors and their effects against a variety of environmental stresses and host nutritional immunity, we will further reveal the complete pathways and the molecular mechanisms of T6SS effectors from a variety of model bacteria in transportation of metal ions (e.g. Zn2+ and Mn2+) by identification of outer membrane receptors and inner membrane transporter proteins which interact directly with these effectors, and are involved in T6SS-mediated ion transportation. Moreover, we will reveal the universality of T6SS in metal ion transportation, investigate the diversity of metal ions transported by T6SS, compare the difference between T6SS and classical metal ion transporters in transportation properties, and explore the possible physiological functions of ion-transporting T6SS. These studies will greatly expand the knowledge on the functions of T6SSs and their effectors, improve the knowledge on bacterial ion transportation mechanisms (especially on transportation mechanisms under low extracellular ion concentrations), and finally lead to a breakthrough in comprehensively understanding of the functions of T6SSs and their effectors.

细菌VI型分泌系统（T6SS）及其效应蛋白的功能研究是当前微生物领域一个新的研究热点。本项目在前期率先发现离子结合型新型T6SS效应蛋白及其对抗多种环境胁迫及宿主营养免疫功能的基础上，进一步以多种重要模式细菌为材料，以对参与离子结合型T6SS效应蛋白转运金属离子的细菌外膜受体蛋白及内膜转运蛋白的鉴定为线索，重点揭示T6SS及其效应蛋白转运Zn2+和Mn2+的途径和机制，系统研究其转运离子功能的普遍性，转运离子种类及方式的多样性，比较其与经典离子转运系统的转运特性差别，并探索其可能具有的广泛生理功能，以拓展当前学术界对细菌VI型分泌系统及其效应蛋白功能的认识，同时完善现有的对细菌离子转运机制（尤其在胞外低离子浓度条件下的转运机制）的认知空白，从而为全面认识T6SS及其效应蛋白的功能带来新的突破。

细菌VI型分泌系统（T6SS）及其效应蛋白的功能研究是当前微生物领域前沿热点。本项目在前期率先发现离子结合型新型T6SS效应蛋白及其对抗环境胁迫及宿主营养免疫功能的基础上，进一步以多种重要模式细菌为材料，以对参与离子结合型T6SS效应蛋白转运金属离子的细菌外膜受体蛋白及内膜转运蛋白的鉴定为线索，揭示了T6SS分泌锰离子结合蛋白通过与外膜锰离子特异转运蛋白MnoT协同转运锰离子以帮助细菌获得生长竞争优势和环境适应能力的机制和途径；揭示了T6SS通过分泌PQS结合型效应蛋白TseF以招募细菌外膜囊泡帮助细菌获取铁的全新的细菌铁获取新途径；揭示了T6SS分泌锌离子结合型效应蛋白通过与外膜血红素转运蛋白协同转运锌离子并抗氧胁迫的途径及开关机制。研究结果在Nature Communications、PNAS、Cell Reports等国际著名期刊发表，并得到Faculty of 1000等的推荐点评，受到国际同行的广泛关注，开辟了该领域一个新的研究方向，并为T6SS抗宿主营养免疫和天然免疫，以及细菌外膜囊泡招募机制等领域带来了重大突破。