title: Antibiotic-induced expression of a cryptic cpb2 gene in equine beta2-toxigenic Clostridium perfringens.
abstract: The cpb2 gene of beta2-toxigenic Clostridium perfringens isolated from horses, cattle, sheep, human and pigs was sequenced. The cpb2 gene of equine and other non-porcine isolates differed from porcine isolates by the absence of an adenine in a poly A tract immediately downstream of the start codon in all non-porcine C. perfringens strains. This deletion involved formation of a cryptic gene harbouring a premature stop codon after only nine amino acid codons, while the full beta2-toxin protein consists of 265 amino acids. Immunoblots carried out with antibodies directed against a recombinant beta2-toxin showed the absence of expression of the beta2-toxin in equine and the other non-porcine strains under standard culture conditions. However, treatment of C. perfringens with the aminoglycosides gentamicin or streptomycin was able to induce expression of the cpb2 gene in a representative equine strain of this group, presumably by frameshifting. The presence of the beta2-toxin was revealed by immunohistology in tissue samples of small and large intestine from horses with severe typhlocolitis that had been treated before with gentamicin. This result may explain the finding that antibiotic treatment of horses affected by beta2-toxigenic C. perfringens leads to a more accentuated and fatal progression of equine typhlocolitis. Clinical observations show a reduced appearance of strong typhlocolitis in horses with intestinal complications admitted to hospital care since the standard use of gentamicin has been abandoned. This is the first report on expression of a bacterial toxin gene by antibiotic-induced ribosomal frameshifting.
authors.affiliation: Institute of Veterinary Bacteriology, Universität Bern, Laenggasstrasse 122, CH-3012 Bern, Switzerland.
authors.forename: Edy M
authors.initials: EM
authors.lastname: Vilei
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Schlatter
authors.forename: Vincent
authors.initials: V
authors.lastname: Perreten
authors.forename: Reto
authors.initials: R
authors.lastname: Straub
authors.forename: Michel R
authors.initials: MR
authors.lastname: Popoff
authors.forename: Maryse
authors.initials: M
authors.lastname: Gibert
authors.forename: Andrea
authors.initials: A
authors.lastname: Gröne
authors.forename: Joachim
authors.initials: J
authors.lastname: Frey
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D002417:Cattle; D003015:Clostridium Infections / Q000382:microbiology / Q000503:physiopathology / Q000662:veterinary; D003016:Clostridium perfringens / Q000187:drug effects / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D003092:Colitis / Q000382:microbiology / Q000503:physiopathology / Q000662:veterinary*; D015964:Gene Expression Regulation, Bacterial; D005839:Gentamicins / Q000494:pharmacology; D006734:Horse Diseases / Q000382:microbiology / Q000503:physiopathology*; D006736:Horses; D006801:Humans; D008969:Molecular Sequence Data; D017422:Sequence Analysis, DNA; D013307:Streptomycin / Q000494:pharmacology; D013552:Swine
chemical_list: D000900:Anti-Bacterial Agents; D001427:Bacterial Toxins; D005839:Gentamicins; C109896:cpb2 protein, Clostridium perfringens; D013307:Streptomycin