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 clinic...
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Frontiers Media S.A.
2021-12-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2021.771945/full |
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author | Prasad Thomas Prasad Thomas Mostafa Y. Abdel-Glil Mostafa Y. Abdel-Glil Mostafa Y. Abdel-Glil Anbazhagan Subbaiyan Anne Busch Inga Eichhorn Lothar H. Wieler Lothar H. Wieler Heinrich Neubauer Mathias Pletz Christian Seyboldt |
author_facet | Prasad Thomas Prasad Thomas Mostafa Y. Abdel-Glil Mostafa Y. Abdel-Glil Mostafa Y. Abdel-Glil Anbazhagan Subbaiyan Anne Busch Inga Eichhorn Lothar H. Wieler Lothar H. Wieler Heinrich Neubauer Mathias Pletz Christian Seyboldt |
author_sort | Prasad Thomas |
collection | DOAJ |
description | 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. |
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spelling | doaj.art-e49919e78a2f469cb3e69a22730f263e2022-12-21T23:11:18ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2021-12-011210.3389/fmicb.2021.771945771945First Comparative Analysis of Clostridium septicum Genomes Provides Insights Into the Taxonomy, Species Genetic Diversity, and Virulence Related to Gas GangrenePrasad Thomas0Prasad Thomas1Mostafa Y. Abdel-Glil2Mostafa Y. Abdel-Glil3Mostafa Y. Abdel-Glil4Anbazhagan Subbaiyan5Anne Busch6Inga Eichhorn7Lothar H. Wieler8Lothar H. Wieler9Heinrich Neubauer10Mathias Pletz11Christian Seyboldt12Institute of Bacterial Infections and Zoonoses, Friedrich-Loeffler-Institut, Jena, GermanyDivision of Bacteriology and Mycology, ICAR-Indian Veterinary Research Institute, Izatnagar, IndiaInstitute of Bacterial Infections and Zoonoses, Friedrich-Loeffler-Institut, Jena, GermanyInstitute for Infectious Diseases and Infection Control, Jena University Hospital – Friedrich Schiller University, Jena, GermanyDepartment of Pathology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, EgyptDivision of Bacteriology and Mycology, ICAR-Indian Veterinary Research Institute, Izatnagar, IndiaDepartment of Anaesthesiology and Intensive Care Medicine, University Hospital Jena, Jena, GermanyDepartment of Veterinary Medicine, Institute of Microbiology and Epizootics, Freie Universität Berlin, Berlin, GermanyDepartment of Veterinary Medicine, Institute of Microbiology and Epizootics, Freie Universität Berlin, Berlin, GermanyRobert Koch Institute, Berlin, GermanyInstitute of Bacterial Infections and Zoonoses, Friedrich-Loeffler-Institut, Jena, GermanyInstitute for Infectious Diseases and Infection Control, Jena University Hospital – Friedrich Schiller University, Jena, GermanyInstitute of Bacterial Infections and Zoonoses, Friedrich-Loeffler-Institut, Jena, GermanyClostridium 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.https://www.frontiersin.org/articles/10.3389/fmicb.2021.771945/fullClostridium septicumcomparative analysisgenomegas gangreneDSM 7534Tvirulence factors |
spellingShingle | Prasad Thomas Prasad Thomas Mostafa Y. Abdel-Glil Mostafa Y. Abdel-Glil Mostafa Y. Abdel-Glil Anbazhagan Subbaiyan Anne Busch Inga Eichhorn Lothar H. Wieler Lothar H. Wieler Heinrich Neubauer Mathias Pletz Christian Seyboldt First Comparative Analysis of Clostridium septicum Genomes Provides Insights Into the Taxonomy, Species Genetic Diversity, and Virulence Related to Gas Gangrene Frontiers in Microbiology Clostridium septicum comparative analysis genome gas gangrene DSM 7534T virulence factors |
title | First Comparative Analysis of Clostridium septicum Genomes Provides Insights Into the Taxonomy, Species Genetic Diversity, and Virulence Related to Gas Gangrene |
title_full | First Comparative Analysis of Clostridium septicum Genomes Provides Insights Into the Taxonomy, Species Genetic Diversity, and Virulence Related to Gas Gangrene |
title_fullStr | First Comparative Analysis of Clostridium septicum Genomes Provides Insights Into the Taxonomy, Species Genetic Diversity, and Virulence Related to Gas Gangrene |
title_full_unstemmed | First Comparative Analysis of Clostridium septicum Genomes Provides Insights Into the Taxonomy, Species Genetic Diversity, and Virulence Related to Gas Gangrene |
title_short | First Comparative Analysis of Clostridium septicum Genomes Provides Insights Into the Taxonomy, Species Genetic Diversity, and Virulence Related to Gas Gangrene |
title_sort | first comparative analysis of clostridium septicum genomes provides insights into the taxonomy species genetic diversity and virulence related to gas gangrene |
topic | Clostridium septicum comparative analysis genome gas gangrene DSM 7534T virulence factors |
url | https://www.frontiersin.org/articles/10.3389/fmicb.2021.771945/full |
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