光杆菌P. asymbiotica Tc细菌毒素对真核宿主细胞作用机制的研究

革兰氏阴性杆菌是人类感染性疾病的常见病原菌，这些病原菌可通过分泌毒力因子，作用于宿主细胞，导致感染性疾病的发生。近期的研究发现Tc细菌毒素（Toxin complex）广泛分布于包括人类致病菌在内的多种革兰氏阴性菌中，提示该毒素很可能在病原菌致病方面起重要作用。目前，Tc细菌毒素在人类相关病原菌致病机制中是否起作用尚不清楚。我们前期研究显示，临床分离的光杆菌P. asymbiotica分泌的Tc细菌毒素具有细胞杀伤活性，而且该类细菌毒素也广泛存在于耶尔森氏菌和沙门氏菌中。本研究将以光杆菌P. asymbiotica为模式生物，阐明其编码的Tc细菌毒素对真核细胞的分子作用机制以及其相关的结构生物学特征。在此基础上，初步筛选与该类细菌毒素相互作用的真核细胞受体及相应的细胞通路。通过研究该类细菌毒素的通用作用机制，可以拓展对病原菌分子致病机制的认识，为进一步控制细菌性感染提供实验依据。

Gram-negative bacteria are common pathogens for human infectious diseases, which could secret virulent effectors to target at host cells for infectious diseases. Recently, it was reported that Tcs (Toxin complexs) are widely distributed among Gram-negative bacteria, including human pathogens, which imply that these toxins may be important for bacterial pathogenicity. However, it is still not clear if these toxins are involved in pathogenicity to human and how it works. Our previous data showed that, Tc toxin secreted by Photorhabdus asymbiotica, an isolated strain from patient, not only exhibited cytotoxic activity, but also are widely encoded in Yersinia and Salmonella. In this study, we will use Photorhabdus asymbiotica as a model to elucidate the mechanism of Tc toxin’s effect on eukaryotic cells and its protein structural characters. Further, eukaryotic receptor binding to Tc toxin along with its cellular pathway will be screened. This general pathogenic mechanism of Tc toxin involved in the interaction between bacteria and host would lead to further understanding of bacterial molecular pathogenicity for experimental basis of infectious diseases control.