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Source: ONE News -
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American medical researchers are using a breakthrough by a New Zealand state science company to develop a new generation of antibiotics that do not provoke bacterial resistance.
Industrial Research Ltd's (IRL) carbohydrate chemistry team discovered that a specific enzyme interfered with "quorum sensing" - the process by which bacteria communicate with each other by producing and detecting signalling molecules known as "auto-inducers".
These molecules coordinate bacterial gene expression and regulate processes -- including virulence - and studies have shown bacterial strains defective in quorum sensing cause less-serious infections.
IRL scientists Richard Furneaux, Gary Evans, and Peter Tyler last year published a paper with researchers at a private university in New York's Bronx on inhibiting pneumonia bacteria using the mechanism.
"These classes of compounds are also useful as anti-cancer agents, in slightly-different compounds," Furneaux said.
Other aggressive bacteria which cause forms of pneumonia, meningitis, and "golden staph" night also be susceptible.
"We've licensed this intellectual property to a start-up company called Pico Pharmaceuticals - we're trying to help them get started and it's quite exciting," said Furneaux.
Pico planned to develop and initiate clinical trials, and Furneaux said there would have to be some "pretty big money" invested in the development work.
In the meantime, producing experimental amounts of the compounds for trials could potentially provide work for IRL's glyco-synthesis biological reactor and production cells.
IRL built the $7 million glyco-synthesis "small molecule drug design" laboratories at Lower Hutt to extract more value from its skills in designing and synthesising carbohydrates.
It has already bid to manufacture experimental quantities of the drugs for Pico, but involvement in this prototype manufacturing would be subject to commercial negotiations, Furneaux said.
Since their joint study with IRL, the American researchers at the Albert Einstein College of Medicine of Yeshiva University have developed compounds used against two notorious microbes, according to a study described in Nature Chemical Biology.
They were vibrio cholerae, which causes cholera and E. coli 0157:H7, the food contaminant that each year causes hundreds of deaths in Europe and North America, particularly where livestock are raised on intensive grain diets.
Most antibiotics initially work extremely well, killing more than 99.9% of microbes they target. But through mutation and the selection pressure exerted by the antibiotic, a few bacterial cells inevitably manage to survive, repopulate the bacterial community, and flourish as antibiotic-resistant strains.
Professor Vern Schramm, and Ruth Merns, the chairwoman of biochemistry at the Einstein medical school, said that antibiotics that could reduce the infective functions of bacteria, but not kill them, will minimise the risk that resistance would later develop.
Rather than killing vibrio cholerae and E. coli 0157:H7, the researchers are targeting the bacterial enzyme, MTAN, identified by Prof Schramm's collaborators at IRL as directly involved in synthesizing the autoinducers crucial to quorum sensing.
Their plan is to find something which will "lock up" MTAN and inhibit it from fuelling quorum sensing.
Schramm has previously synthesised other compounds to lock up enzymes of interest.
One, forodesine, blocks an enzyme that triggers T-cell malignancies in a clinical study treating a form of leukaemia.
In the Nature Chemical Biology study, Schramm's team tested three compounds over 26 generations of both bacteria, and found the 26th generations were as sensitive to the antibiotics as the first.
"We call these agents everlasting antibiotics," Schramm said.
The American researchers have now developed more than 20 potent MTAN inhibitors, all of which are expected to be safe for human use because blocking a bacterial enzyme would have no effect on human metabolism.
