Binary toxin-producing, large clostridial toxin-negative Clostridium difficile strains are enterotoxic but do not cause disease in hamsters.
Binary toxin CDT or its genes have been identified in some strains of Clostridium difficile that also produce the large clostridial toxins, toxins A and B (A+B+CDT+), including a newly recognized epidemic strain in the United States and Canada. To study the effects of binary toxin alone, we characterized 4 binary toxin CDT-positive only (A-B-CDT+) C. difficile strains. Unlike other clostridial binary toxins, binary toxin CDT required exogenous trypsin for activation. Supernatants from all A-B-CDT+ strains caused marked fluid accumulation in the rabbit ileal loop assay after concentration and trypsinization. In addition, the ileal loop response was neutralized by antisera raised against other binary toxin-producing clostridia. Challenge of clindamycin-treated hamsters with these strains resulted in colonization but not diarrhea or death. Binary toxin CDT may play an adjunctive role to toxins A and B in the pathogenesis of C. difficile-associated disease but by itself may not be sufficient to cause disease.
Geric
Barbara
B
Department of Biology, University of Ljubljana, Ljubljana, Slovenia.
Carman
Robert J
RJ
Rupnik
Maja
M
Genheimer
Christopher W
CW
Sambol
Susan P
SP
Lyerly
David M
DM
Gerding
Dale N
DN
Johnson
Stuart
S
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000145:classification / Q000378:metabolism*; D001427:Bacterial Toxins / Q000096:biosynthesis / Q000145:classification / Q000378:metabolism*; D002981:Clindamycin / Q000008:administration & dosage; D016360:Clostridioides difficile / Q000472:pathogenicity* / Q000502:physiology*; D006224:Cricetinae; D004195:Disease Models, Animal; D004761:Enterocolitis, Pseudomembranous / Q000382:microbiology; D004768:Enterotoxins / Q000096:biosynthesis / Q000145:classification / Q000378:metabolism*; D005243:Feces / Q000382:microbiology; D007082:Ileum / Q000473:pathology; D007106:Immune Sera / Q000378:metabolism; D007422:Intestines / Q000382:microbiology; D008647:Mesocricetus; D011817:Rabbits; D014357:Trypsin / Q000378:metabolism
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004768:Enterotoxins; D007106:Immune Sera; C035598:enterotoxin, Clostridium; C031815:toxB protein, Clostridium difficile; D002981:Clindamycin; D014357:Trypsin