title: Clostridium difficile: New Insights into the Evolution of the Pathogenicity Locus.
abstract: 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".
authors.affiliation: Laboratoire Pathogenèse des Bactéries Anaérobies, Institut Pasteur, Paris, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Monot
authors.affiliation: AP-HP, Hôpital Saint Antoine National Reference Laboratory for C. difficile, Paris, France.|UPMC Univ Paris 06, GRC n°2, Epidiff, Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Eckert
authors.affiliation: AP-HP, Hôpital Saint Antoine National Reference Laboratory for C. difficile, Paris, France.|UPMC Univ Paris 06, GRC n°2, Epidiff, Paris, France.
authors.forename: Astrid
authors.initials: A
authors.lastname: Lemire
authors.affiliation: Laboratoire Pathogenèse des Bactéries Anaérobies, Institut Pasteur, Paris, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Hamiot
authors.affiliation: Laboratoire Pathogenèse des Bactéries Anaérobies, Institut Pasteur, Paris, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Dubois
authors.affiliation: AP-HP, Hôpital Saint Antoine National Reference Laboratory for C. difficile, Paris, France.|UPMC Univ Paris 06, GRC n°2, Epidiff, Paris, France.
authors.forename: Carine
authors.initials: C
authors.lastname: Tessier
authors.affiliation: CH, Hôpital Cambrai, Cambrai, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Dumoulard
authors.affiliation: Hôpital de Villefranche-sur-Saône, Villefranche-sur-Saône, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Hamel
authors.affiliation: AP-HP, Hôpital Saint Antoine National Reference Laboratory for C. difficile, Paris, France.|UPMC Univ Paris 06, GRC n°2, Epidiff, Paris, France.
authors.forename: Amandine
authors.initials: A
authors.lastname: Petit
authors.affiliation: AP-HP, Hôpital Saint Antoine National Reference Laboratory for C. difficile, Paris, France.|UPMC Univ Paris 06, GRC n°2, Epidiff, Paris, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Lalande
authors.affiliation: Plate-forme Génomique, Institut Pasteur, Paris, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Ma
authors.affiliation: Plate-forme Génomique, Institut Pasteur, Paris, France.
authors.forename: Christiane
authors.initials: C
authors.lastname: Bouchier
authors.affiliation: AP-HP, Hôpital Saint Antoine National Reference Laboratory for C. difficile, Paris, France.|UPMC Univ Paris 06, GRC n°2, Epidiff, Paris, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Barbut
authors.affiliation: Laboratoire Pathogenèse des Bactéries Anaérobies, Institut Pasteur, Paris, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Dupuy
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D001427:Bacterial Toxins / Q000235:genetics* / Q000378:metabolism; D016360:Clostridioides difficile / Q000145:classification / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity*; D004768:Enterotoxins / Q000235:genetics* / Q000378:metabolism; D019143:Evolution, Molecular; D015964:Gene Expression Regulation, Bacterial; D056426:Genetic Loci; D044404:Genomic Islands; D006801:Humans; D010802:Phylogeny; D017422:Sequence Analysis, DNA; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004768:Enterotoxins; C041348:tcdA protein, Clostridium difficile; C031815:toxB protein, Clostridium difficile