艰难梭菌是一种产孢子的专性厌氧菌，是一种厚壁菌门梭菌属的条件致病菌。在正常的人体肠道菌群遭到破坏后，艰难梭菌得以定殖并造成包括伪膜性肠炎、腹泻等在内的肠道疾病，严重时危及生命。目前艰难梭菌感染（CDI）已经成为了一个全球公共健康问题，每年都造成数百万的感染病例和数以万计的死亡。艰难梭菌的致病机理取决于其表达的外毒素，尤其TcdB是艰难梭菌感染的决定性致病因子。我们前期的研究发现TcdB存在多种亚型（包含了至少两种尚未研究过的分支），并且以TcdB1和TcdB2为例验证了亚型间存在明显的毒理和致病性差别。本研究旨先以基因组分析、生物信息学和大数据处理为基础对TcdB进行系统性的亚型分类分析，之后以生化和分子生物学、细胞生物学和动物实验为基础进行TcdB亚型毒理和病理的分析和研究。我们相信本研究无论是对艰难梭菌毒素机制的理解和认识，还是对艰难梭菌感染的临床诊断和治疗都有着重要的意义。

Clostridioides difficile is a spore-forming anaerobic bacterium, which belongs to the family of Firmicutes. C. difficile is a typical opportunistic pathogen. Disruption of normal gut flora by antibiotics allows C. difficile to colonize the colon, leading to diarrhea and life-threatening pseudomembranous colitis. C. difficile infection (CDI) has gradually become a worldwide health problem, leading to millions of cases and thousands of death every year. TcdB is the most critical virulence factor for the bacterium during the infection. Our preliminary study showed that TcdB has multiple variants (including at least two new branches). Studies on TcdB1 and TcdB2 further suggested that the different TcdB subtypes has notable difference in toxicology and pathogenic potentials. In this study, we aim to systematically investigate the subtypes of TcdB, and compare the pathogenesis caused by the different toxin subtypes. We firmly believe that this study will help to better understand the pathogenesis of CDI, and provide important guidance to the clinal diagnosis and therapy of this disease.