NEW YORK (Reuters Health) - A group of scientists from Australia have developed a nonpathogenic Shiga toxin-binding probiotic that completely protected mice challenged with a lethal dose of Shiga toxin-producing E. coli, according to a report in the May 1st issue of the Journal of Infectious Diseases.
The probiotic binds to and neutralizes the two major Shiga toxin types - Stx1 and Stx2 - with “extraordinary avidity,” write the authors. Twice daily oral administration of the construct protected the mice.
Unlike an earlier version of the probiotic, this refined version is suitable for human trials for the treatment and/or prevention of potentially life-threatening enteric infections resulting from E. coli O157:H7, report Dr. James C. Paton and colleagues from the School of Molecular and Biomedical Science at the University of Adelaide.
The team had previously constructed a novel Stx-binding compound consisting of recombinant E. coli expressing two Neisseria galactosyl transferase genes that protected animals from virulent toxin-producing strains.
However, this construct is “unlikely to be approved for human trials,” they acknowledge, because the host strain is derived from an E. coli clinical isolate and the plasmid used for expression contains an antibiotic-resistance gene.
“The present [construct] addresses regulatory issues by modifying the host bacterium to make it safer, and by removing an antibiotic resistance gene from the plasmid required for expression of the toxin-binding molecules on the bacterial surface,” Dr. Paton told Reuters Health.
Importantly, these modifications to the host-vector system “required for licensure” have not compromised the protective efficacy of the probiotic, the team reports. The plasmid is “stably maintained,” according to the researchers, and the construct neutralizes Shiga toxin and provides 100% protection from highly virulent toxin-producing E. coli in mice.
“This landmark study has very broad applications,” Dr. Paton said. “In addition to Shiga toxigenic E. coli (including O157:H7), related products can be developed [using this method] for cholera, travelers’ diarrhea, [and] pseudomembranous colitis,” he said.
Source: J Infect Dis 2004;189:1547-1555. [ Google search on this article ]
MeSH Headings:Escherichia coli O157: ProbioticsCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
