产气荚膜梭菌是鸡坏死性肠炎的主要致病菌，一般在肉鸡养殖抗生素休药期内易发，严重威胁养鸡业的健康发展。产气荚膜梭菌致病因子较多，有文献报道NetB可裂解肠上皮细胞并导致坏死性肠炎，是与鸡坏死性肠炎直接相关的重要毒力因子。本课题组前期研究中已在国内分离到多株致病性产气荚膜梭菌，并扩增到NetB编码基因，进一步实现了NetB的原核表达和纯化，根据NetB成孔活性过程中其空间构象变化特性，进行了抑制剂的筛选并获得了多种有效天然化合物，其中以桑色素抑制活性最强。在此基础上，本项目拟通过化学生物学相关实验阐明桑色素和NetB相互作用的分子机制；细胞感染实验和实验动物感染实验分别在体内外验证桑色素对产气荚膜梭菌感染的防治作用，以期为防治鸡坏死性肠炎，尤其是休药期内鸡坏死性肠炎的新药研发提供新的策略和先导化合物。

Clostridium perfringens is the main causative agent of chicken necrotic enteritis (CNE), which usually affected broilers during the withdrawal period, seriously threatening the healthy development of the poultry industry. Clostridium perfringens produces a variety of virulence factors and necrotic enteritis B-like toxin (NetB), a pore-forming toxin that lyses intestinal epithelial cells, is an essential virulence factor associated with avian necrotic enteritis caused by Clostridium perfringens. We have previously isolated various pathogenic Clostridium perfringens strains and identified the gene encoding NetB in these strains. Some natural compounds have been identified as effective inhibitors of NetB by hemolysis assay, in which morin has the highest inhibitory activity. Based on previous results, this study is intended to further determine the protective effect of morin against Clostridium perfringens virulence in vitro and in vivo via cell-bacteria co-culture system and chicken model of infection. Moreover, the molecular mechanism of morin against NetB activity would be characterized by molecular dynamics simulations, site directed mutation and MST. Together, this study would provide new leading compounds and novel strategy for the development of drug for chicken necrotic enteritis, especially those during the withdrawal period.