Effect of shigella enterotoxin 1 (ShET1) on rabbit intestine in vitro and in vivo.
BACKGROUND
Shigella enterotoxin 1 is a novel enterotoxin elaborated by Shigella flexneri 2a that causes fluid accumulation in rabbit ileal loops and a rise in short circuit current in Ussing chambers.


OBJECTIVE
To gain insights into the mechanism of action of shigella enterotoxin 1.


METHODS
Supernatants from genetically engineered clones either overexpressing shigella enterotoxin 1 or producing deletion mutants of the toxin were tested in rabbit ileum both in vitro and in vivo.


RESULTS
In rabbit ileum shigella enterotoxin 1 induced an irreversible rise in short circuit current that was not mediated by any of the recognised intracellular mediators of secretion. Deletion of 90% of the A subunit of the holotoxin ablated its enterotoxicity. In the in vivo perfusion model, the toxin induced a time dependent decrease in water absorption, whereas no changes were detected in the segment perfused with supernatants obtained from the deletion mutant. Finally, partially purified toxin induced a dose dependent increment in short circuit current that reached its plateau at a toxin concentration of 4 x 10(-6) M.


CONCLUSIONS
Shigella enterotoxin 1 induces a time and dose dependent intestinal secretion in the rabbit animal model, suggesting that it may be responsible for the watery phase of Shigella flexneri 2a infection.
Fasano
A
A
Division of Pediatric, Gastroenterology and Nutrition, University of Maryland, School of Medicine, Baltimore 21201, USA.
Noriega
F R
FR
Liao
F M
FM
Wang
W
W
Levine
M M
MM
D000818:Animals; D001427:Bacterial Toxins / Q000494:pharmacology*; D003967:Diarrhea / Q000378:metabolism / Q000382:microbiology*; D004305:Dose-Response Relationship, Drug; D004405:Dysentery, Bacillary / Q000378:metabolism*; D004594:Electrophysiology; D004768:Enterotoxins / Q000494:pharmacology*; D007082:Ileum / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D007408:Intestinal Absorption / Q000187:drug effects*; D009924:Organ Culture Techniques; D011817:Rabbits; D012763:Shigella flexneri / Q000737:chemistry*; D013997:Time Factors; D014867:Water / Q000378:metabolism
D001427:Bacterial Toxins; D004768:Enterotoxins; D014867:Water