There’s a war going on, and most of us can’t even see it. Man has been battling microbes for millennia, and despite their microscopic size, the bugs have been winning. But man may finally have a leg up, scientists from Canada and the U.K. say—and it's all thanks to a humble fungus.
While antibiotics have been a powerful weapon against bacteria that can cause serious and even fatal infections, the microbes have been just as busy as drug makers in finding ways to evade the medications. What’s more, the man-made compounds also appear to pose little challenge to bacteria, which are surrounded by such molecules, made by their neighbors, other microbes or other organisms in their environments. “Bacteria seem to laugh in their face,” says Gerard Wright, director of the Michael G. DeGroote Institute for Infectious Disease Research at McMaster University and the new study’s senior author. The result? Most antibiotics, including penicillin and the carbapenems that have been introduced more recently, contain a chemical ring that bacteria have been remarkably adept at breaking. Once compromised, the ring and the antibiotic are neutralized.
So most drug companies have tried to develop stronger, or slightly different chemical rings, but Wright and his colleagues decided to tackle the problem from a different tack. Why not disrupt the enzyme that the bacteria were using to disable the antibiotics instead?
It’s an old approach that most pharmaceutical companies have abandoned, since the strategy requires combining an antibiotic with something that disables the bacteria’s ability to resist the drug±two drugs means twice the potential complications and side effects, so most large-scale efforts have focused on building better solo antibiotics.
But aware that nature is a rich resource of organisms that naturally make compounds that can interfere with bacterial enzymes, Andrew King in Wright’s lab screened 500 such molecules and found one, from Aspergillus versicolor, that worked remarkably well in inhibiting New Delhi Metallobeta-Lactamase-1 (NDM-1), an antibiotic resistant gene that the World Health Organization recently called a global public health threat. (He also tested 30,000 synthetic compounds and none inhibited NDM-1.)
“Natural products, and especially natural products that come from microbes like bacteria and fungi, are privileged molecules, in the sense that they are products of evolution themselves, so they are much better at interacting with bacteria,” says Wright, who published his results in the journal Nature. Rather than being relatively simple and flat, like the compounds created in labs, these agents are three-dimensional with structures and functions that are difficult to recreate in a petri dish. “If we want to look for inhibitors of antibiotic resistance on a significant scale, we need to go back to these sources,” he says.
The fungus turns out to be one of the most resilient organisms on the planet, able to survive in the harsh climates of the arctic, the salty Dead Sea and even the International Space Station. That hardiness also makes it among the most common molds in damp or water-damaged buildings and moist air ducts.
When Wright and his team tested the fungus in mice infected with lethal doses of K. pneumoniae that carried the NDM-1 resistance to antibiotics, the mice shrugged off the infection. In fact, the fungus allowed the antibiotic to work effectively again, essentially circumventing the bacteria’s attempt at resisting the drug.
“The idea of rescuing our old antibiotics, is something that folks are starting to realize is not only a good idea, but doable,” he says. He and his team hope to find similar inhibitors to neutralize resistance against the other major classes of antibiotics, but as optimistic as Wright is about the strategy, he admits that ultimately the bacteria may find ways to resist even these agents. “Resistance is a natural phenomenon’ it’s just natural selection. There’s no way to get around it.” Except perhaps to stay one step ahead of the microbes and find compounds that can thwart them…again and again.