imu scientist land huge breakthrough

Last Update: Thursday, October 5, 2006. 6:25pm
Scientists claim gastro breakthrough
Scientists from Adelaide University have made what they claim is a world breakthrough in understanding how bacterial toxins cause severe gastro diseases.

Professor James Paton, who heads the university's microbiology unit, says the research, which involved scientists from Monash University and the United States, resulted from the discovery of a potent toxin.

He says the breakthrough may also provide better treatments for age-related and degenerative diseases, such as Parkinson's and Alzheimer's.

"It works by attacking one of the components of cells which is involved in packaging of proteins," he said.

"So by studying the effects of this toxin on normal cells we may well get insights into better treatments for things like Alzheimer's or Parkinson's."

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Back in 2000 Adrienne Paton, James Paton and Renato Morona, who we'll nickname the 'RMT Dream Team',
cracked an important problem concerning E. Coli and related pathogenic bacteria. These bugs make a human or an
animal sick by emitting toxins that get into cells on the mucosal surfaces of the gut wall and interfere with the cell's
ability to transfer fluids to the rest of the body. As a consequence, fluid in the gut has to be flushed out through a
bout of diarrhoea, which if not checked can lead to dehydration and potentially death. Bacterial toxins can cause this
fluid transfer problem because the effected cells have on their surfaces receptor molecules made out of various kinds
of sugar collectively called glycosyls, which the toxins use as a gateway into the cell. The RMT Dream Team, when
struggling with the question of how to protect people against a bacterial toxin known as Shiga, came up with an
elegant solution to the problem - why not genetically engineer harmless versions of E. Coli, of which there are many
to choose from, to produce on their surfaces mimics of the very receptor molecules favoured by Shiga toxins? That
way, the engineered E. Coli could soak up the toxins, keeping the gut relatively sound in terms of its fluid handling
ability while allowing the immune system of the subject being treated to deal with the pathogenic versions of the
bug. In effect, the engineered E. Coli would form a ‘missile defense shield for the
gut’ in that the toxin ‘missiles’ launched by pathogenic bacteria would be
intercepted by the engineered E. Coli so that it couldn’t score a direct hit in the gut
wall. Shiga-emitting bacteria, such as the dreaded Shigella dysenteriae, or a
version of E. Coli called STEC (short for 'Shiga Toxin producing E. Coli'), would
in this situation find no reason to evolve to avoid an antibiotic of some sort, and
would continue to happily emit toxins unaware that their toxin-production efforts
were in vain. The RMT Dream Team achieved its breakthrough by searching
through gene databases looking for the kind of structures to which toxins such as
Shiga bound, finding them among the genomes for other bacteria such as N.
gonorrhoeae (evidently bacterial toxins evolved over the eons during ongoing
warfare between various single-cells organisms). What the Dream Team wanted was DNA encoding enzymes that
would create those toxin receptor structures at the ends of lipopolysccharides, that is, combination fat and sugar
molecules, also to be found within the source bacteria. These enzymes, called glycosyltransferases, were with some
modifications engineered into a harmless version of E. Coli. When the engineered E. Coli was administered to mice
that were then challenged with which what would otherwise be a fatal dose of STEC, the result was 100% protection
for the mice. Subsequent work published later in 2000 showed that chemically killed versions of the engineered E.
Coli could achieve the same end and be orally available. By 2003 the RMT Dream Team had developed two
products suitable for use in pigs, one to treat a disease called post-weaning colibacillosis, and another to tackle socalled
porcine oedema. Post weaning colibacillosis is an E. Coli toxin-induced affliction to which pigs are
particularly susceptible in an intensive production environment. Porcine oedema, less common but more deadly, is a
disease where the relevant toxins damage blood vessels in the pig, resulting in its sudden death.