Of Mice and Men

"It's kind of cool. 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."
Gerry Wright, microbiologist, McMaster University, Hamilton

Joe Raedle/Getty Images files   Antibiotic resistance is one of the biggest challenges facing medical practitioners right now, but a new discovery by McMaster researchers may help doctors fight back against the genetic adaptations plaguing many of the world's primary medicines for treating bacterial infections.

 

The recent spate of reports out of hospitals stricken with the onset of deadly microbial organisms that have transformed themselves to become resistant to antibiotics are considered to be "nightmare" bacteria. They've appeared in Ontario, Quebec, Alberta and British Columbia in hospital outbreaks. Their evolution from organisms that could be destroyed with the use of antibiotics to biochemically become resistant to those antibiotics, has surfaced as a menace to human health.

The World Health Organization warned in the spring of "devastating" consequences for human health in the face of unsuccessful struggles from within the medical-science community to find solutions for these new antibiotic superbugs. With few new strains of antibiotics coming along through pharmaceutical research, something other than laboratory-produced antibiotics has now surfaced.

A research team of scientists at Hamilton's McMaster university has taken a fungus common to Nova Scotia and discovered in it a potentially powerful new weapon that may very well succeed in overcoming the newest, most fearful microbes on Earth. The fungus contains a molecule which the McMaster team isolated, and with its use killed "superbugs" resistance to antibiotics.

Handout/Canadian Press   Aspergillus versicolor, a fungus contained in a soil sample from Nova Scotia, is shown in a handout photo. The fungus produces a compound, called AMA, which inhibits the antibiotic-resistance powers the NDM-1 gene gives bacteria in which it is found. Researchers at McMaster University in Hamilton hope the compound can eventually be used in combination with antibiotics to override drug resistance.

Aspergillomarasmine A (or AMA) is a molecule that clutches a protein inside the bacteria and then "rips out" zinc, thus rendering the superbugs defenceless against the powerful antibiotics its evolutionary bioengineering had succeeded in enabling it to resist. The researchers had teamed up with a British microbiologist to reveal that the fungal extract had a similar effect on over 200 superbugs that have been alarming the medical community around the world.

The researchers demonstrated that with the use of the fungal compound in combination with an antibiotic, laboratory mice infected with a lethal strain of resistant pneumonia could be saved from death. The findings were reported in the journal Nature. Presenting as an "excellent example" of the way nature's own bioactive compounds can "breathe new life" into existing antibiotics, according to Bob Hancock of University of British Columbia, himself engaged in the search for alternate ways to combat superbugs.

AMA happened to be revealed in a common soil fungus from Nova Scotia. It represented one of ten thousand organisms Dr. Wright has made use of in the creation of his "collection of brown goo". Each of those ten thousand organisms naturally produces 24 to 40 bioactive compounds; molecules that produce "these wonderful shapes that can bind to proteins and receptors in cells". These are molecules, he points out that nature "crafted by evolution over millions of years".

Dr. Wright had asked one of his graduate students to screen the ten thousand samples to look for molecules that could help kill superbugs with the enzyme that makes them resistant to carbapenem, a class of last-resort antibiotics widely used in hospitals. Serendipitously, the graduate student discovered AMA in the first of the 500 mixtures he sampled. "He just lucked out", laughed Dr. Wright.

The next step was to isolate and purify the compound and from there to demonstrate how AMA, combined with meropenem, a carbapenem antibiotic type, could kill lethal resistant organisms. Working in tandem with Tim Walsh at Cardiff University, 229 strains of resistant bacteria isolated from patients around the world over the last decade, were tested with AMA. In combination with meropenem, AMA restored antibiotic susceptibility in 88 percent of the bacteria tested.

Mice infected with a lethal, resistant strain of pneumonia, after a single treatment of AMA combined with meropenem, survived. Superbugs use the zinc ions on bacterial enzymes to inactivate carbapenem antibiotics. AMA, by ripping out the zinc, leaves the microbes vulnerable to destruction from the antibiotic activity: AMA is a "rapid and potent" inhibitor of the enzyme that demonstrates "resistance can be overcome and antibiotic activity fully restored".

What works on mice is assumed to work on human beings as well. From research to trials to acceptance on success and final use throughout the Globe, another weapon in the battle against microbial agents causing diseases that destroy life.