title: Horizontal gene transfer converts non-toxigenic Clostridium difficile strains into toxin producers.
abstract: Clostridium difficile is a major nosocomial pathogen and the main causative agent of antibiotic-associated diarrhoea. The organism produces two potent toxins, A and B, which are its major virulence factors. These are chromosomally encoded on a region termed the pathogenicity locus (PaLoc), which also contains regulatory genes, and is absent in non-toxigenic strains. Here we show that the PaLoc can be transferred from the toxin-producing strain, 630Δerm, to three non-toxigenic strains of different ribotypes. One of the transconjugants is shown by cytotoxicity assay to produce toxin B at a similar level to the donor strain, demonstrating that a toxigenic C. difficile strain is capable of converting a non-toxigenic strain to a toxin producer by horizontal gene transfer. This has implications for the treatment of C. difficile infections, as non-toxigenic strains are being tested as treatments in clinical trials.
authors.affiliation: Department of Microbial Diseases, UCL Eastman Dental Institute, University College London, 256 Gray's Inn Road, London WC1X 8LD, UK.
authors.forename: Michael S M
authors.initials: MS
authors.lastname: Brouwer
authors.forename: Adam P
authors.initials: AP
authors.lastname: Roberts
authors.forename: Haitham
authors.initials: H
authors.lastname: Hussain
authors.forename: Rachel J
authors.initials: RJ
authors.lastname: Williams
authors.forename: Elaine
authors.initials: E
authors.lastname: Allan
authors.forename: Peter
authors.initials: P
authors.lastname: Mullany
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D001427:Bacterial Toxins / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival; D016360:Clostridioides difficile / Q000235:genetics* / Q000378:metabolism; D003227:Conjugation, Genetic; D004768:Enterotoxins / Q000235:genetics* / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000382:microbiology; D015964:Gene Expression Regulation, Bacterial; D022761:Gene Transfer, Horizontal; D016680:Genome, Bacterial; D006801:Humans
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; C488583:Clostridium difficile lethal toxin B; D004768:Enterotoxins; C041348:tcdA protein, Clostridium difficile