A graduate student out for a hike in Nova Scotia 10 years ago picked up some dirt for her professor’s side project.
Today, a fungus in that dirt may provide a treatment for a nearly untreatable hospital infection that the Centers for Disease Control and Prevention calls “the nightmare bacteria.”
The musty fungus, Aspergillus versicolor, produces a chemical commonly known as AMA, short for Aspergillomarasmine, which de-claws the resistant bacteria. Scientists at McMaster University in Hamilton, Ontario, recovered AMA during a decade-long effort to collect natural chemicals.
“It was a crazy fishing expedition, but it was grounded in some reality,” said Gerry Wright, director of the Michael G. DeGroote Institute for Infectious Disease Research at McMaster University.
Each year, 2 million people are infected with antibiotic-resistant bacteria in the United States, and 23,000 of them die. The nightmare bacteria, known to science as Carbapenem Resistant Enterobacteriaceae, represent a small segment of those infections, 9,000.
CRE is more dangerous than old foes like MRSA. It’s impervious to even the most powerful antibiotics. Over the long term, CRE can teach other bacteria its bag of tricks.
Unless science tricks it first. AMA’s ploy is to deprive the bacteria of zinc, which it needs to fight off antibiotics.
“The 21st century for antibiotics is not going to be like the 20th century,” Wright said. “We have to be very clever in how we do this.”
AMA is just one of an estimated 200,000 to 300,000 chemicals that Wright extracted from 500 soil samples. The dirt, mostly from around Canada, was corralled into lunch bags over 10 years. Each gram contains more than one billion different microbes.
Wright said he could spend a lifetime studying just one gram of dirt.
“These are the product of evolution. Organisms are making them for a reason,” Wright said. “These compounds are tailor-made to interact with biology.”
For the study, published Wednesday in Nature, scientists threw 500 of the chemical extracts at a strain of CRE to see if any of them affected the bacteria’s defenses.
AMA seemed to work. In the next step, mice were injected with a lethal dose of CRE. But when they were treated with a combination of AMA and an antibiotic, the mice survived.
Drug companies are not rushing to produce new antibiotics. Few are in development to address broadly resistant bacteria, said Amanda Jezek, vice president of public policy and government relations for the Infectious Diseases Society of America.
“We remain very concerned about the state of antibiotic R&D,” Jezek said. “Scientifically, the low-hanging fruit has been plucked.”
There’s also little money in antibiotics research. Wright said he financed his study with leftover money from other projects and relied on lab members to collect samples whenever they were out traveling.
“You can’t get money to do this,” Wright said. “I’ve been doing it on the sly with leftover cash.”
Saul Hymes, assistant professor of clinical pediatrics at Stony Brook Children’s Hospital Division of Pediatric Infectious Diseases in New York, said the discovery of AMA is a useful step to fight infections that are “next to impossible to treat.”
“These bugs are a major problem. Any new piece of ammunition that we may have now or a few years down the line are definitely encouraging,” Hymes said. “Who’s to say that in other fungi out there, there aren’t other similar agents?”
The current mix of drugs in Hymes’ arsenal can’t defeat CRE’s antibiotic-chewing enzymes. Last-resort methods use brute force – punching holes in the cell membrane – that can be harmful to the patient.
“You’re just dodging the resistance mechanism entirely,” Hymes said.
It’s also just one piece of the nightmare-bacteria puzzle. AMA affects only a strain of CRE that’s endemic in Asia, called NDM-1. It has no effect on KPC, the Klebsiella that’s more often found in American hospitals.
“In terms of global impact right now, the NDM-1 story is the bigger one. In terms of the story in hospitals in North America, right now, it’s a combination,” Wright said.
There’s another possible speed bump. Because AMA deprives the bacteria of zinc, it also affects zinc-dependent enzymes in the body. One of those enzymes, ACE, needs zinc to control blood pressure.
So far, tests on mice showed that the compound wasn’t toxic. Wright said he hopes to hit a “sweet spot” so it doesn’t affect humans adversely.
“It’s the one thing that could derail this compound, if it shows toxicity,” Wright said. “But so far so good.”
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