杀鱼爱德华氏菌CpxA-CpxR双组分系统响应抗菌肽铁调素调控VI型分泌系统表达和功能的机制研究

杀鱼爱德华氏菌是重要的水产养殖病原菌，由其引起的爱德华氏菌病已对世界范围内海水养殖产业造成巨大危害。VI型分泌系统(T6SS)是该菌关键毒力因子，对其在宿主体内存活、复制以及致病起着重要作用。抗菌肽铁调素作为该菌天然宿主大菱鲆天然免疫应答的重要组分，在大菱鲆抵御杀鱼爱德华氏菌感染过程中发挥关键作用。申请人前期利用转座子插入测序技术发现，杀鱼爱德华氏菌T6SS的表达受CpxA-CpxR双组分系统调控。CpxA-CpxR广泛存在于革兰氏阴性菌中，参与对抗菌肽的应答。因此，本项目拟对CpxA-CpxR双组分系统响应抗菌肽铁调素调控T6SS表达和功能的分子机制进行研究，包括CpxA感知铁调素、进而CpxR调控T6SS表达以及最终T6SS抑制宿主天然免疫应答和铁调素合成并降解已合成铁调素的完整分子机制。研究结果将为阐明病原菌响应宿主信号调控毒力因子的感染机制提供新的视角，加深对其致病机制的认识。

Edwardsiella piscicida, a Gram-negative intracellular pathogen, has been recognized as one of the leading pathogens worldwide aquaculture, causing enormous economic losses. During its infection of host cells, type VI secretion system (T6SS) plays an essential role and contributes to bacterial survival, colonization and infection. As a key component of the host innate immune response, antimicrobial peptide hepcidin modulates the bacterial load and prevents the establishment of an infection caused by pathogens, which is used as a defense strategy by turbot. Our preliminary results indicated that in E. piscicida the expression of T6SS was regulated by CpxA-CpxR, a two-component system. Given that CpxA-CpxR was identified to confer bacterial resistance to antimicrobial peptide in many pathogens, we are aim to elucidate the exact role of CpxA-CpxR in response to hepcidin, including that CpxA senses hepcidin signal; then CpxR activates the expression of T6SS; eventually T6SS effectors inhibit host innate immune response and hepcidin synthesis and also degrade hepcidin. Taken together, these findings will help us deeply understand the relationship of host environmental signal and bacterial virulence system, which will provide a new perspective for the development of high-efficiency vaccines.