Published: June 25, 2014
A lowly soil fungus from Nova Scotia has provided scientists with a powerful new weapon against some of the most alarming microbes on the planet.
A molecule, which a team at McMaster University plucked from the fungus, is enabling them to kill “superbugs” resistant to antibiotics.
The molecule, aspergillomarasmine A or AMA, latches on to a protein inside the bacteria and “rips out” zinc rendering the superbugs defenceless against powerful antibiotics it could previously resist, says microbiologist Gerry Wright, who heads the team in Hamilton, Ont.
Once they uncovered AMA, the researchers teamed up with a British microbiologist and showed the fungal extract had the same effect on more than 200 superbugs that have been causing misery around the world.
Then to underscore AMA’s promise, the researchers showed that by using the fungal compound in combination with an antibiotic protected lab mice infected with an otherwise lethal strain of resistant pneumonia.
Scientists says the findings, to be reported Thursday in the Journal Nature, offer hope in the battle against resistant bacteria causing growing international alarm.
It’s an “excellent example” of the way naturally bioactive compounds can “breathe new life” into existing antibiotics, says Bob Hancock, at the University of B.C., who is also searching for ways to stop superbugs.
Resistant organisms can now evade even last resort antibiotics — a class of drugs called carbapenems. While still rare in Canada, these so-called “nightmare” bacteria have shown up in Ontario, Quebec, Alberta and, most recently, caused an outbreak in B.C.
They have evolved the biochemical machinery to not only withstand antibiotics, but can also readily share their genes for resistance with other common bacteria. The World Health Organization warned this spring of “devastating” consequences for human health if the bugs can’t be stopped.
There are few new antibiotics in the drug pipeline, but AMA shows how nature can provide some relief by coming to the rescue of existing antibiotics.
“It’s kind of cool,” Wright says of the way AMA works in combination with old antibiotics to stop resistant bacteria. “While we’re waiting for new antibiotics to be discovered there is reason to believe we can renew life in some of the old ones.”
AMA was uncovered in a common soil fungus picked up in Nova Scotia — one of 10,000 organisms Wright has used to create what he calls his “collection of brown goo.”
Each of the 10,000 organisms naturally produce between 25 and 40 bioactive compounds — molecules that he says have “these wonderful shapes that can bind to proteins and receptors in cells.”
Unlike synthetic molecules created in the lab, he says the natural compounds have been “crafted by evolution over millions of years.”
To find molecules that might help in the battle against resistant microbes, Wright’s group grows the organisms in the lab and then grinds them up creating the brown mixtures.
His graduate student Andrew King set out to screen the 10,000 samples looking for molecules that would help kill superbugs carrying an enzyme that makes them resistant to carbapenem, an important class of antibiotics widely used in hospitals.
King hit on AMA in the first of the 500 brown goos he sampled. “He just lucked out,” laughs Wright.
Then they isolated and purified the compound and were able to show how AMA, when combined with meropenem, a carbapenem antibiotic, could kill resistant organisms.
Then working with Tim Walsh at Cardiff University they tested AMA on 229 strains of resistant bacteria isolated from patients around the world over the last decade. When used in combination with meropenem, they found that AMA restored antibiotic susceptibility in 88 per cent of the bacteria. And mice infected with a lethal and resistant strain of pneumonia survived after a single treatment of AMA and meropenem.
Wright says the fungal extract latches onto and rips out the zinc ions on the bacterial enzyme that superbugs use to inactivate carbapenem antibiotics. It is a “rapid and potent” inhibitor of the enzyme that shows “resistance can be overcome and antibiotic activity fully restored.”
The McMaster team has taken out a patent on the way AMA inhibits the enzyme, and says it’s an “excellent lead” for a potential new “adjuvant therapy” that could restore the potency of existing antibiotics.
Wright likens AMA’s effect on the superbugs’ enzyme “ to taking out the defender in basketball so you can score the basket.”