Clostridioides difficile toxins (TcdA and TcdB) are major exotoxins responsible for C. difficile infection (CDI) associated diseases. The previously reported TcdB variants showed distinct biological features, immunoactivities, and potential pathogenicity in disease progression. Here, we performed global comparisons of amino acid sequences of both TcdA and TcdB from 3,269 C. difficile genomes and clustered them according to the evolutionary relatedness. We found that TcdB was much diverse and could be divided into eight subtypes, of which four were first described. Further analysis indicates that the tcdB gene undergoes accelerated evolution to maximize diversity. By tracing TcdB subtypes back to their original isolates, we found that the distribution of TcdB subtypes was not completely aligned with the phylogeny of C. difficile. These findings suggest that the tcdB genes not only frequently mutate, but also continuously transfer and exchange among C. difficile strains.

艰难梭菌毒素（TcdA和TcdB）是负责艰难梭菌感染（CDI）相关疾病的主要外毒素。先前报道的TcdB变体在疾病进展中显示出独特的生物学特征，免疫活性和潜在的致病性。在这里，我们对来自3,269个艰难梭菌基因组的TcdA和TcdB的氨基酸序列进行了全局比较， 并根据进化相关性将它们聚类。我们发现TcdB的差异很大，可以分为8个亚型，其中首先描述了4个。进一步分析表明，tcdB基因经历加速进化以最大化多样性。通过追溯TcdB亚型回到其原始分离株，我们发现TcdB亚型的分布与艰难梭菌的系统发育不完全一致。这些发现表明tcdB基因不仅经常突变，而且在艰难梭菌菌株之间也不断地转移和交换。