Clostridium difficile: New Insights into the Evolution of the Pathogenicity Locus

• Published in: Scientific reports Vol. 5; no. 1; p. 15023
• Main Authors: Monot, Marc, Eckert, Catherine, Lemire, Astrid, Hamiot, Audrey, Dubois, Thomas, Tessier, Carine, Dumoulard, Bruno, Hamel, Benjamin, Petit, Amandine, Lalande, Valérie, Ma, Laurence, Bouchier, Christiane, Barbut, Frédéric, Dupuy, Bruno
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08.10.2015; Nature Publishing Group
• Subjects: 45; 45/23; 45/77; 631/181/2474; 631/208/212/748; 631/326/107; 631/326/325/1506; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Bacterial Toxins - genetics; Bacterial Toxins - metabolism; Clostridium difficile - classification; Clostridium difficile - genetics; Clostridium difficile - metabolism; Clostridium difficile - pathogenicity; Enterotoxins - genetics; Enterotoxins - metabolism; Evolution, Molecular; Gene Expression Regulation, Bacterial; Genetic Loci; Genomes; Genomic Islands; Human health and pathology; Humanities and Social Sciences; Humans; Integration; Life Sciences; multidisciplinary; Pathogenicity; Phylogeny; Science; Secretion; Sequence Analysis, DNA; Toxin A; Virulence; Virulence factors; comparative genomic; bacterial gene; clinical microbiology; Clostridium difficile; evolutionary genetics
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep15023

The major virulence factors of Clostridium difficile are toxins A and B. These toxins are encoded by tcdA and tcdB genes, which form a pathogenicity locus (PaLoc) together with three additional genes that have been implicated in regulation ( tcdR and tcdC ) and secretion ( tcdE ). To date, the PaLoc has always been found in the same location and is replaced in non-toxigenic strains by a highly conserved 75/115 bp non-coding region. Here, we show new types of C. difficile pathogenicity loci through the genome analysis of three atypical clinical strains and describe for the first time a variant strain producing only toxin A (A + B − ). Importantly, we found that the PaLoc integration sites of these three strains are located in the genome far from the usual single known PaLoc integration site. These findings allowed us to propose a new model of PaLoc evolution in which two “Mono-Toxin PaLoc” sites are merged to generate a single “Bi-Toxin PaLoc”.