They found it in the soil of Nova Scotia of all places: A recently discovered fungus molecule could hold the key to suppressing a deadly gene’s resistance to many common antibiotics, a new study from McMaster University finds.
The gene is known as NDM-1, or New Delhi Metallo-beta-Lactamase-1. The World Health Organization recognizes it as a global health threat for its ability to confer resistance to one of the most potent classes of antibiotics, known as carbapenems. Among its startling presence in many bacteria strains, NDM-1 has been found in the most commonly encountered bacterium among humans, Escherichia coli — a bacteria that causes more cases of bladder and kidney infections than anything else. Without antibiotics to fight NDM-1, doctors are effectively helpless.
Added to this challenge is how pervasive NDM-1 really is. Carbapenems are a class of drugs very similar to penicillin, which mean they’re used in a variety of unique cases. Worse, NDM-1 infects a range of organisms that, themselves, cause “all sorts of challenging diseases and are multi-drug-resistant already,” explained Gerry Wright, director of the Michael G. DeGroote Institute for Infectious Disease Research at McMaster, in a statement. The gene has been found in contaminated water in Southeast Asia and in clinics around the world, he adds, all of which emphasizes the importance of finding a molecule capable of blocking it.
Before the soil in Nova Scotia was ever mined for its powerful fungus, scientists understood that NMD-1 needs zinc to thrive. The challenge was in finding a way to remove the zinc safely and without causing collateral damage to the patient. With the discovery of the new molecule, called AMA, that extraction may be possible.
To test their hypothesis, the research team infected a group of mice with an NDM-1-expressing superbug. The only mice that survived were ones that had been given a combination of the AMA molecule and a carbapenem antibiotic. Those that received just the molecule or just the antibiotic died. While the findings are positive, Wright concedes there is still much work to do in bringing the solution to a global audience.
"This is public enemy number one," he warned. "It came out of nowhere, it has spread everywhere and has basically killed our last resource of antibiotics, the last pill on the shelf, used to treat serious infections.”
Perhaps the most important part of Wright’s research is understanding what role key fungus molecules play in combating antibiotic resistance. Basically, when a person is sick with infection she’s given antibiotics. But because physicians have been turning to antibiotics so frequently in recent decades — one of the greatest debates raging in medical circles at the moment — certain bacteria have been clever enough to mutate around the drug’s potency and develop resistance. Now scientists are on the counterattack, trying to outdo the bacteria’s outdoing.
There is also the large offensive scientists are mounting against physicians for whom antibiotics are their first line of defense, where, in reality, they should be a last resort. France, for instance, has launched a national program to raise awareness called “Antibiotics are not automatic.” And stateside, there is the “Get smart” program, both of which mirror Canada’s own “Do bugs need drugs?” campaign. Indeed, treating mostly viral infections with drugs that only work on bacteria can do nothing but harm. So, physicians are encouraged to pursue less potent options. Wright and his team believe the latest study may help reduce that risk when antibiotics do turn out to be necessary.
"This will solve one aspect of a daunting problem,” Wright explained. “AMA rescues the activity of carbapenem antibiotics, so instead of having no antibiotics, there will be some. This is a made-in-Canada solution for a global problem."
Source: King A, Reid-Yu S, Wang W, et al. Aspergillomarasmine A overcomes metallo-β-lactamase antibiotic resistance. Nature. 2014.