Data_Sheet_2_First Comparative Analysis of Clostridium septicum Genomes Provides Insights Into the Taxonomy, Species Genetic Diversity, and Virulence Related to Gas Gangrene.PDF

Clostridium septicum is a Gram-positive, toxin-producing, and spore-forming bacterium that is recognized, together with C. perfringens, as the most important etiologic agent of progressive gas gangrene. Clostridium septicum infections are almost always fatal in humans and animals. Despite its clinical and agricultural relevance, there is currently limited knowledge of the diversity and genome structure of C. septicum. This study presents the complete genome sequence of C. septicum DSM 7534T type strain as well as the first comparative analysis of five C. septicum genomes. The taxonomy of C. septicum, as revealed by 16S rRNA analysis as well as by genomic wide indices such as protein-based phylogeny, average nucleotide identity, and digital DNA–DNA hybridization indicates a stable clade. The composition and presence of prophages, CRISPR elements and accessory genetic material was variable in the investigated genomes. This is in contrast to the limited genetic variability described for the phylogenetically and phenotypically related species Clostridium chauvoei. The restriction-modification (RM) systems between two C. septicum genomes were heterogeneous for the RM types they encoded. C. septicum has an open pangenome with 2,311 genes representing the core genes and 1,429 accessory genes. The core genome SNP divergence between genome pairs varied up to 4,886 pairwise SNPs. A vast arsenal of potential virulence genes was detected in the genomes studied. Sequence analysis of these genes revealed that sialidase, hemolysin, and collagenase genes are conserved compared to the α-toxin and hyaluronidase genes. In addition, a conserved gene found in all C. septicum genomes was predicted to encode a leucocidin homolog (beta-channel forming cytolysin) similar (71.10% protein identity) to Clostridium chauvoei toxin A (CctA), which is a potent toxin. In conclusion, our results provide first, valuable insights into strain relatedness and genomic plasticity of C. septicum and contribute to our understanding of the virulence mechanisms of this important human and animal pathogen.

克雷伯菌属的产气荚膜梭菌（Clostridium septicum）是一种革兰氏阳性、产毒并形成孢子的细菌，与产气荚膜梭菌（C. perfringens）一同被视为进行性气性坏疽的最主要致病因素。克雷伯菌属的产气荚膜梭菌感染在人类和动物中几乎总是致命的。尽管其在临床和农业领域具有重要相关性，但目前对克雷伯菌属的产气荚膜梭菌的多样性及基因组结构所知甚少。本研究展示了克雷伯菌属的产气荚膜梭菌DSM 7534T类型菌株的完整基因组序列，以及首次对五个克雷伯菌属的产气荚膜梭菌基因组进行的比较分析。通过16S rRNA分析以及基于蛋白质的谱系、平均核苷酸身份和数字DNA-DNA杂交等全基因组指数揭示的克雷伯菌属的产气荚膜梭菌的分类学表明，其属于一个稳定的类群。在所研究的基因组中，前噬菌体、CRISPR元件和辅助遗传物质的组成和存在存在差异，这与在分类学和表型上相关的物种产气荚膜梭菌（Clostridium chauvoei）所描述的有限遗传变异性形成对比。两个克雷伯菌属的产气荚膜梭菌基因组之间的限制修饰（RM）系统在RM类型编码方面表现出异质性。克雷伯菌属的产气荚膜梭菌具有开放的全基因组，包含2,311个基因，其中1,429个为辅助基因。基因组对之间的核心基因组单核苷酸多态性（SNP）差异高达4,886个。在所研究的基因组中检测到大量潜在的致病基因。对这些基因的序列分析表明，与α毒素和透明质酸酶基因相比，唾液酸酶、溶血素和胶原蛋白酶基因在保守性上较高。此外，所有克雷伯菌属的产气荚膜梭菌基因组中发现的保守基因被预测编码一种类似白细胞毒素（beta通道形成细胞毒素）的蛋白，其与产气荚膜梭菌毒素A（CctA）相似（蛋白质序列同源性为71.10%），而CctA是一种强效毒素。总之，我们的研究结果首次为我们提供了克雷伯菌属的产气荚膜梭菌菌株相关性和基因组可塑性的宝贵见解，并有助于我们理解这一重要的人类和动物病原体的致病机制。