A soil sample from a national park in eastern Canada
 has produced a compound that appears to reverse
 antibiotic resistance in dangerous bacteria.














Scientists at McMaster University in Ontario
 discovered that the compound almost instantly
 turned off a gene in several harmful bacteria that
makes them highly resistant to treatment with a
class of antibiotics used to fight so-called
superbug infections. The compound, called
 aspergillomarasmine A, or AMA, was extracted
 from a common fungus found in soil and mold.


Antibiotic resistance is a growing public-
health threat. Common germs such
asEscherichia coli, or E. coli, are becoming
 harder to treat because they increasingly
don't respond to antibiotics. Some two million
people in the U.S. are infected each year by
 antibiotic-resistant bacteria and 23,000 die
as a result, according to the Centers for
Disease Control and Prevention. The
 World Health Organization has called
antibiotic resistance a threat to global
public health.
The Canadian team was able to
disarm a gene—New Delhi Metallo
-beta-Lactamase-1, or NDM-1—that
 has become "public enemy No. 1" since
its discovery in 2009, says Gerard Wright,
 director of McMaster's Michael G.
DeGroote Institute for Infectious Disease
 Research and lead researcher on the
 study. The report appears on the cover
 of this week's issue of the journal Nature.
"Discovery of a fungus capable of
rendering these multidrug-resistant
organisms incapable of further infection
is huge," says Irena Kenneley, a
microbiologist and infectious disease
specialist at Frances Payne Bolton
 School of Nursing at Cleveland's
 Case Western Reserve University.
 "The availability of more treatment
 options will ultimately save many
more lives," says Dr. Kenneley, who
wasn't involved in the McMaster research.
The McMaster team plans further
experiments to determine the safety
and effective dosage of AMA. It could
take as long as a decade to complete
clinical trials on people with superbug
infections, Dr. Wright says













The researchers found that AMA,
 extracted from a strain of
Aspergillus versicolor and combined
 with a carbapenem antibiotic,
inactivated the NDM-1 gene in
three drug-resistant superbugs
—Enterobacteriaceae, a group of
bacteria that includes E. coli;Acenitobacter,
 which can cause pneumonia and
blood infections; and Pseudomonas,
which often infect patients in hospitals
and nursing homes. The NDM-1 gene
 encodes an enzyme that helps bacteria
 become resistant to antibiotics and that
requires zinc to survive. AMA works by
removing zinc from the enzyme, freeing
the antibiotic to do its job, Dr. Wright says.
 Although AMA was only tested on
carbapenem-resistant bacteria, he
expects the compound would have
 a similar effect when combined with
other antibiotics.
AMA was first identified in the 1960s in
 connection with leaf wilt in plants and
later investigated as a potential drug for
treating high blood pressure. The
compound turned up in Dr. Wright's
lab a few years ago during a random
screening of organisms derived from
 10,000 soil samples stored at McMaster.
The sample that produced AMA was
 collected by one of Dr. Wright's graduate
 students during a visit to a Nova Scotia
park. It was the only sample of 500 tested
 that inhibited NDM-1 in cell cultures.
"It was a lucky hit," says Dr. Wright. "It tells
 us that going back to those environmental
 organisms, where we got antibiotics in the
 first place, is a really good idea."
The McMaster team developed a purified
form of AMA for experiments on mice injected
 with a lethal form of drug-resistant pneumonia.
 Treatment with either AMA or a carbapenem
antibiotic alone proved ineffective. But combining
 the substances resulted in more than 95% of
 the mice still being alive after five days. The
 combination was also tested on 229 cell cultures
 from human patients infected with resistant
superbugs. The treatment resensitized 88%
 of the samples to carbapenem.
Still, bacteria could someday find a way to
outwit AMA. "I can't imagine anything we could
 make where resistance would never be an
issue," he says. "At the end of the day, this
 is evolution and you can't fight evolution."