Clostridium perfringens is associated with a variety of diseases in both humans and animals. Recent advances in genomic sequencing make it timely to re-visit this important pathogen. Although the genome sequence of C. perfringens was first determined in 2002, large-scale comparative genomics with isolates of different origins is still lacking. In this study, we used whole-genome sequencing of 45 C . perfringens isolates with isolation time spanning an 80‐year period and performed comparative analysis of 173 genomes from worldwide strains. We also conducted phylogenetic lineage analysis and introduced an openness index (OI) to evaluate the openness of bacterial genomes. We classified all these genomes into five lineages and hypothesized that the origin of C. perfringens dates back to ~80 000 years ago. We showed that the pangenome of the 173 C . perfringens strains contained a total of 26 954 genes, while the core genome comprised 1020 genes, accounting for about a third of the genome of each isolate. We demonstrated that C. perfringens had the highest OI compared with 51 other bacterial species. Intact prophage sequences were found in nearly 70.0 % of C. perfringens genomes, while CRISPR sequences were found only in ~40.0 %. Plasmids were prevalent in C. perfringens isolates, and half of the virulence genes and antibiotic resistance genes (ARGs) identified in all the isolates could be found in plasmids. ARG-sharing network analysis showed that C. perfringens shared its 11 ARGs with 55 different bacterial species, and a high frequency of ARG transfer may have occurred between C. perfringens and species in the genera Streptococcus and Staphylococcus . Correlation analysis showed that the ARG number in C. perfringens strains increased with time, while the virulence gene number was relative stable. Our results, taken together with previous studies, revealed the high genome openness and genetic diversity of C. perfringens and provide a comprehensive view of the phylogeny, genomic features, virulence gene and ARG profiles of worldwide strains.

中文翻译：

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系统发育和基因组分析揭示了产气荚膜梭菌的高度基因组开放性和遗传多样性


产气荚膜梭菌与人类和动物的多种疾病有关。基因组测序的最新进展使得我们及时重新审视这种重要的病原体。尽管产气荚膜梭菌的基因组序列于2002年首次确定，但仍缺乏不同来源分离株的大规模比较基因组学。在这项研究中，我们使用了 45 C的全基因组测序。分离时间跨越 80 年的产气荚膜杆菌菌株，并对来自世界各地菌株的 173 个基因组进行了比较分析。我们还进行了系统发育谱系分析，并引入开放性指数（OI）来评估细菌基因组的开放性。我们将所有这些基因组分为五个谱系，并假设产气荚膜梭菌的起源可以追溯到约 8 万年前。我们展示了 173 C的全基因组。产气荚膜杆菌菌株总共包含26 954个基因，而核心基因组包含1020个基因，约占每个分离株基因组的三分之一。我们证明，与其他 51 种细菌相比，产气荚膜梭菌具有最高的 OI。在近 70.0% 的产气荚膜梭菌基因组中发现了完整的原噬菌体序列，而仅在约 40.0% 的基因组中发现了 CRISPR 序列。质粒在C中普遍存在。 产气荚膜杆菌分离株中，所有分离株中鉴定出的毒力基因和抗生素抗性基因（ARG）有一半可以在质粒中找到。 ARG共享网络分析表明，产气荚膜梭菌与55种不同的细菌物种共享其11个ARG，并且产气荚膜梭菌与链球菌属和葡萄球菌属的物种之间可能发生高频率的ARG转移。相关分析表明，产气荚膜梭菌菌株中ARG数量随时间增加而增加，而毒力基因数量相对稳定。我们的结果与之前的研究相结合，揭示了产气荚膜梭菌的高度基因组开放性和遗传多样性，并提供了全球菌株的系统发育、基因组特征、毒力基因和 ARG 图谱的全面视图。