Probing genomic aspects of the multi-host pathogen Clostridium perfringens reveals significant pangenome diversity, and a diverse array of virulence factors

Raymond Kiu, Shabhonam Caim, Sarah Alexander, Purnima Pachori, Lindsay J. Hall*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)

Abstract

Clostridium perfringens is an important cause of animal and human infections, however information about the genetic makeup of this pathogenic bacterium is currently limited. In this study, we sought to understand and characterise the genomic variation, pangenomic diversity, and key virulence traits of 56 C. perfringens strains which included 51 public, and 5 newly sequenced and annotated genomes using Whole Genome Sequencing. Our investigation revealed that C. perfringens has an "open" pangenome comprising 11667 genes and 12.6% of core genes, identified as the most divergent single-species Gram-positive bacterial pangenome currently reported. Our computational analyses also defined C. perfringens phylogeny (16S rRNA gene) in relation to some 25 Clostridium species, with C. baratii and C. sardiniense determined to be the closest relatives. Profiling virulence-associated factors confirmed presence of well-characterised C. perfringens-associated exotoxins genes including a-toxin (plc), enterotoxin (cpe), and Perfringolysin O (pfo or pfoA), although interestingly there did not appear to be a close correlation with encoded toxin type and disease phenotype. Furthermore, genomic analysis indicated significant horizontal gene transfer events as defined by presence of prophage genomes, and notably absence of CRISPR defence systems in > 70% (40/56) of the strains. In relation to antimicrobial resistance mechanisms, tetracycline resistance genes (tet) and anti-defensins genes (mprF) were consistently detected in silico (tet: 75%; mprF: 100%). However, pre-antibiotic era strain genomes did not encode for tet, thus implying antimicrobial selective pressures in C. perfringens evolutionary history over the past 80 years. This study provides new genomic understanding of this genetically divergent multi-host bacterium, and further expands our knowledge on this medically and veterinary important pathogen.

Original languageEnglish
Article number2485
JournalFrontiers in Microbiology
Volume8
Issue numberDEC
DOIs
Publication statusPublished - 12 Dec 2017

Bibliographical note

Funding Information:
This work was supported by a Wellcome Trust Investigator Award to LH (100974/C/13/Z) and support of the Biotechnology and Biological Sciences Research Council (BBSRC) Institute Strategic Programme grant for Gut Health and Food Safety BB/J004529/1 (LH). RK is a PhD student at the Norwich Medical School of University of East Anglia (UEA), partially funded by UEA international bursary (Faculty of Medical and Health Sciences). NCTC3000 project is funded by the Wellcome Trust (101503/Z/13/Z). Funders had no input into the design of the study, analysis, or interpretation of the data, or in writing the manuscript.

Publisher Copyright:
© 2017 Kiu, Caim, Alexander, Pachori and Hall.

Keywords

  • Antimicrobial resistance
  • Clostridial infection
  • Clostridium perfringens
  • Exotoxins
  • Genomics
  • Pangenome
  • Whole genome sequencing

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