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BMC microbiology2016; 16; 41; doi: 10.1186/s12866-016-0653-3

Comparative genomic analysis of toxin-negative strains of Clostridium difficile from humans and animals with symptoms of gastrointestinal disease.

Abstract: Clostridium difficile infections (CDI) are a significant health problem to humans and food animals. Clostridial toxins ToxA and ToxB encoded by genes tcdA and tcdB are located on a pathogenicity locus known as the PaLoc and are the major virulence factors of C. difficile. While toxin-negative strains of C. difficile are often isolated from faeces of animals and patients suffering from CDI, they are not considered to play a role in disease. Toxin-negative strains of C. difficile have been used successfully to treat recurring CDI but their propensity to acquire the PaLoc via lateral gene transfer and express clinically relevant levels of toxins has reinforced the need to characterise them genetically. In addition, further studies that examine the pathogenic potential of toxin-negative strains of C. difficile and the frequency by which toxin-negative strains may acquire the PaLoc are needed. Results: We undertook a comparative genomic analysis of five Australian toxin-negative isolates of C. difficile that lack tcdA, tcdB and both binary toxin genes cdtA and cdtB that were recovered from humans and farm animals with symptoms of gastrointestinal disease. Our analyses show that the five C. difficile isolates cluster closely with virulent toxigenic strains of C. difficile belonging to the same sequence type (ST) and have virulence gene profiles akin to those in toxigenic strains. Furthermore, phage acquisition appears to have played a key role in the evolution of C. difficile. Conclusions: Our results are consistent with the C. difficile global population structure comprising six clades each containing both toxin-positive and toxin-negative strains. Our data also suggests that toxin-negative strains of C. difficile encode a repertoire of putative virulence factors that are similar to those found in toxigenic strains of C. difficile, raising the possibility that acquisition of PaLoc by toxin-negative strains poses a threat to human health. Studies in appropriate animal models are needed to examine the pathogenic potential of toxin-negative strains of C. difficile and to determine the frequency by which toxin-negative strains may acquire the PaLoc.
Publication Date: 2016-03-12 PubMed ID: 26971047PubMed Central: PMC4789261DOI: 10.1186/s12866-016-0653-3Google Scholar: Lookup
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  • Comparative Study
  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article studies the genomes of five toxin-free Clostridium difficile strains from humans and animals showing symptoms of gastrointestinal disease in Australia. The analysis suggests that these strains are similar to toxic strains, which might indicate a threat to human health if these toxin-free strains acquire the toxin-producing gene.

Background and Significance

  • The research paper is centered around studying toxin-negative strains of Clostridium difficile infections (CDI), a prevalent health problem in humans and food animals. The significance of this research stems from the potential of these strains to acquire the pathogenicity locus (PaLoc) that encodes ToxA and ToxB, two primary virulence factors of C. difficile, thus possibly turning toxic and threatening human health.

Research Objectives and Methodology

  • The researchers sought to thoroughly characterize toxin-negative strains of C. difficile genetically and to understand the possibility of them acquiring the PaLoc.
  • The research team conducted a comparative genomic analysis of five Australian toxin-free isolates of C. difficile from humans and farm animals showing gastrointestinal disease symptoms. The isolates lacked tcdA, tcdB, and both binary toxin genes cdtA and cdtB.

Key Findings

  • The results revealed that the toxin-negative C. difficile isolates are pretty similar to virulent toxigenic strains belonging to the same sequence type (ST) regarding their virulence gene profiles.
  • It was also noted that phage acquisition, or the process of phages (viruses that infect bacteria) adding their genetic material into the bacterial genome, played a significant role in the evolution of C. difficile.

Conclusion and Implications

  • The findings suggest that the global C. difficile population includes six clades, each containing both toxin-positive and toxin-negative strains.
  • The data implies that toxin-negative strains of C. difficile might harbor a variety of putative virulence factors similar to those seen in toxigenic variants, indicating a potential health risk if these strains acquire the PaoLoc.
  • Additional studies using suitable animal models are encouraged to investigate the pathogenic potential of toxin-negative C. difficile strains and the likelihood of these strains acquiring the PaLoc.

Cite This Article

APA
Roy Chowdhury P, DeMaere M, Chapman T, Worden P, Charles IG, Darling AE, Djordjevic SP. (2016). Comparative genomic analysis of toxin-negative strains of Clostridium difficile from humans and animals with symptoms of gastrointestinal disease. BMC Microbiol, 16, 41. https://doi.org/10.1186/s12866-016-0653-3

Publication

ISSN: 1471-2180
NlmUniqueID: 100966981
Country: England
Language: English
Volume: 16
Pages: 41
PII: 41

Researcher Affiliations

Roy Chowdhury, Piklu
  • The ithree institute, University of Technology Sydney, Sydney, 2007, Australia. Piklu.Bhattacharya@uts.edu.au.
  • NSW Department of Primary Industries, Elizabeth Macarthur Agricultural Institute, PMB 8, Camden, NSW, 2570, Australia. Piklu.Bhattacharya@uts.edu.au.
DeMaere, Matthew
  • The ithree institute, University of Technology Sydney, Sydney, 2007, Australia.
Chapman, Toni
  • NSW Department of Primary Industries, Elizabeth Macarthur Agricultural Institute, PMB 8, Camden, NSW, 2570, Australia.
Worden, Paul
  • The ithree institute, University of Technology Sydney, Sydney, 2007, Australia.
Charles, Ian G
  • The ithree institute, University of Technology Sydney, Sydney, 2007, Australia.
  • Institute of Food Research, Norwich Research Park, Colney, Norwich, NR4 7UA, UK.
Darling, Aaron E
  • The ithree institute, University of Technology Sydney, Sydney, 2007, Australia.
Djordjevic, Steven P
  • The ithree institute, University of Technology Sydney, Sydney, 2007, Australia. Steven.Djordjevic@uts.edu.au.

MeSH Terms

  • Amino Acid Sequence
  • Animals
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Bacterial Toxins / metabolism
  • Clostridioides difficile / classification
  • Clostridioides difficile / genetics
  • Clostridioides difficile / isolation & purification
  • Clostridioides difficile / metabolism
  • Clostridium Infections / microbiology
  • Clostridium Infections / veterinary
  • Gastrointestinal Diseases / microbiology
  • Gastrointestinal Diseases / veterinary
  • Horse Diseases / microbiology
  • Horses
  • Humans
  • Molecular Sequence Data
  • Phylogeny
  • Sequence Alignment
  • Swine
  • Swine Diseases / microbiology

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Citations

This article has been cited 7 times.
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