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

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.

Clostridium septicum myonecrosis in a pediatric patient with a self-reported penicillin allergy

Infections with Clostridium septicum are especially rare in pediatric patients. C. septicum is the most common cause of spontaneous myonecrosis and is usually associated with comorbid malignancy. Treatment of choice for cases of C. septicum myonecrosis is prompt and thorough surgical debridement and antimicrobial therapy with high dose penicillin. The experience and management of C. septicum infections in patients who are unable to take penicillin are not well described, and the optimal duration of therapy is largely unknown. We describe a case of spontaneous myonecrosis in a 14-year-old receiving cytotoxic chemotherapy for Burkitt’s lymphoma who had an anecdotal history of a penicillin allergy. Her infection was initially treated with ceftazidime and metronidazole in concert with debridement but was ultimately cured with 3 weeks of intravenous penicillin therapy following a graded penicillin challenge in hospital. We observed a delayed inflammatory tissue response to a C. septicum skin, soft tissue infection that temporally corresponded to neutrophil reconstitution in our patient with severe neutropenia. Our experience demonstrates that C. septicum myonecrosis can present indolently and progress rapidly and highlights the need for clinical vigilance and repeat “second-look” surgeries. Our case also emphasizes the importance of de-labelling penicillin allergies.

Clostridium septicum-induced gangrene in the right lower extremity complicating pneumatosis in the right ventricle and the pulmonary artery and occlusion of right femoral artery: a case report

Background Gas gangrene is usually manifested as myonecrosis and subcutaneous gas accumulation, but rarely manifested as arterial occlusion or pneumatosis in the right ventricle and the pulmonary artery. Case presentation We report a case of gas gangrene caused by Clostridium septicum. The patient developed gas gangrene after being pecked by a chicken but turned for the better following antibiotic treatment and debriment. Imaging test revealed a rare occlusion of the right femoral artery and pneumatosis in the right ventricle and the main pulmonary artery. Conclusions In the presence of gas gangrene, special care must be taken to prevent against the formation of circulatory air embolism. The gas gangrene-induced gangrene in the limb of this patient might be attributed to the combined action of infection and arterial occlusion. MDT (Multidisciplinary team)-Green Channel mode is conductive to treatment success of gas gangrene.