Evolutionary history of the Clostridium difficile pathogenicity locus

Area of Science:

• Microbiology
• Evolutionary Biology
• Genetics

Background:

• Clostridium difficile infection symptoms stem from toxins produced by the pathogenicity locus (PaLoc).
• The PaLoc's variable presence and clade specificity suggest a mobile genetic element, despite its stable chromosomal location.
• Understanding PaLoc's evolutionary history is crucial for explaining its complex behavior.

Purpose of the Study:

• To reconstruct the evolutionary history of the Clostridium difficile pathogenicity locus (PaLoc).
• To investigate the mobility and integration patterns of the PaLoc and associated genetic elements like Tn6218.

Main Methods:

• Phylogenetic analyses of C. difficile core genomes and PaLoc regions.
• Annotation of genomic regions spanning the PaLoc in a diverse isolate collection.
• Comparative genomics to trace the acquisition, exchange, and loss of the PaLoc.

Main Results:

• Distinct PaLoc variants were acquired clade-specifically after strain divergence, with recent acquisition in clade 4.
• Homologous recombination mediated rare exchanges and losses of PaLoc DNA, with a recent loss event ~30 years ago.
• The clade 3 PaLoc contained the novel transposon Tn6218, which was frequently mobilized and sometimes carried antibiotic resistance genes.

Conclusions:

• The PaLoc exhibits rare mobilization via homologous recombination, contrasting with the frequent transposition of Tn6218.
• Tn6218 elements, derived from Tn916, are nonconjugative but contribute to antibiotic resistance dissemination.
• The evolutionary dynamics of the PaLoc and Tn6218 provide insights into C. difficile virulence and adaptation.