Table_1_First Comparative Analysis of Clostridium septicum Genomes Provides Insights Into the Taxonomy, Species Genetic Diversity, and Virulence Related to Gas Gangrene.XLSX

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.

产气荚膜梭菌（Clostridium septicum）是一种革兰氏阳性、产生毒素并形成孢子的细菌，与产气荚膜梭菌（C. perfringens）一同被认为是进行性气性坏疽的最重要病因。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意义，但目前对产气荚膜梭菌的多样性和基因组结构仍知之甚少。本研究展示了产气荚膜梭菌DSM 7534T标准菌株的完整基因组序列，以及首次对五个产气荚膜梭菌基因组进行的比较分析。通过16S rRNA分析和基于蛋白质的系统发育、平均核苷酸身份以及数字DNA-DNA杂交等全基因组指标揭示的产气荚膜梭菌的分类学表明，其属于一个稳定的类群。所研究基因组中前噬菌体、CRISPR元件和辅助遗传物质的组成及存在情况各不相同，这与表型相关且系统发育相近的物种产气荚膜梭菌（Clostridium chauvoei）所描述的有限遗传变异性形成鲜明对比。两个产气荚膜梭菌基因组之间的限制性修饰（RM）系统在编码的RM类型上表现出异质性。产气荚膜梭菌具有开放的全基因组，其中包含2,311个核心基因和1,429个辅助基因。基因组对之间的核心基因组SNP差异高达4,886个成对SNP。在所研究的基因组中检测到了大量潜在的致病基因。对这些基因的序列分析显示，与α毒素和透明质酸酶基因相比，唾液酸酶、溶血素和胶原酶基因是保守的。此外，在所有产气荚膜梭菌基因组中发现的一个保守基因被预测编码一种类似（蛋白质序列同源性为71.10%）产气荚膜梭菌毒素A（CctA）的白细胞溶解素同源物（β通道形成细胞毒素）。产气荚膜梭菌毒素A是一种强效毒素。总之，我们的研究结果首次为我们提供了关于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畜共患病原体的致病机制。