Data_Sheet_4_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.

艰难梭菌（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最重要的致病因子。艰难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，但关于艰难梭菌的多样性和基因组结构的知识目前仍然有限。本研究呈现了艰难梭菌DSM 7534T型菌株的完整基因组序列，以及首次对五个艰难梭菌基因组的比较分析。通过16S rRNA分析以及基于蛋白质系统发育、平均核苷酸一致性和数字DNA-DNA杂交等全基因组指标，揭示了艰难梭菌的税率稳定。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存在差异，这与形态和系统发育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鲜明对比。两个艰难梭菌基因组之间的限制修饰（RM）系统在编码的RM类型上存在异质性。艰难梭菌具有开放的全基因组，其中包含2,311个基因，代表核心基因，以及1,429个辅助基因。基因组对之间的核心基因SNP差异高达4,886个成对SNPs。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是保守的。此外，在所有艰难梭菌基因组中发现的保守基因被预测编码一种类似溶白素（beta通道形成细胞毒素）的蛋白，其与产气荚膜梭菌毒素A（CctA）具有相似性（71.10%的蛋白同源性），而CctA是一种强效毒素。总之，我们的研究结果首次为艰难梭菌的菌株相关性和基因组塑性提供了宝贵的见解，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。