Subtyping analysis reveals new variants and accelerated evolution of Clostridioides difficile toxin B
Subtyping analysis reveals new variants and accelerated evolution of Clostridioides difficile toxin B
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亚型分析揭示艰难梭菌毒素 B 的新变异和加速进化
DOI：
10.1038/s42003-020-1078-y
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发表时间：
2020-07-03
影响因子：
5.9
通讯作者：
Tao, Liang
中科院分区：
文献类型：
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作者：
Shen, Enhui;Zhu, Kangli;Tao, Liang
艰难梭菌毒素（clostridiides difficile toxin， TcdA和TcdB）是导致艰难梭菌感染（CDI）相关疾病的主要外毒素。先前报道的TcdB变异在疾病进展中显示出不同的生物学特征、免疫活性和潜在的致病性。在这里，我们对3269c的TcdA和TcdB的氨基酸序列进行了全局比较。艰难梭菌基因组，并根据进化亲缘关系将它们聚类。我们发现TcdB的多样性很大，可以分为8个亚型，其中4个是首次描述的。进一步分析表明，tcdB基因经历了加速进化以最大化多样性。通过追踪TcdB亚型到其原始分离株，我们发现TcdB亚型的分布与艰难梭菌的系统发育并不完全一致。这些发现表明，tcdB基因不仅频繁突变，而且在艰难梭菌菌株之间不断转移和交换。Shen等人比较了3269个艰难梭菌基因组中细菌毒素TcdA和TcdB的氨基酸序列，鉴定出四种新的TcdB亚型。他们发现TcdB的氨基酸序列比TcdA更多样化。这项研究表明，tcdB基因不仅频繁突变，而且在艰难梭菌菌株之间不断转移和交换。
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 3,269C. 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. Shen et al. compare the amino acid sequences of bacterial toxins TcdA and TcdB from 3,269 Clostridioides difficile genomes to identify four new TcdB subtypes. They find that TcdB was more diverse in amino acid sequence than TcdA. This study suggests that the tcdB genes not only frequently mutate, but they also continuously transfer and exchange among C. difficile strains.