66 DISCOVERMAGAZINE.COM
results made a deep impression on the
ield. “It’s one of those papers that
unveils a whole new area of research,”
gushed McMaster University
biochemist Gerry Wright at the time.
But unveiling the ubiquity of antibiotic
eating only deepened the mystery. “The
irst paper in 2008 was ‘gee whiz, that’s
surprising,’ ” Wright says in retrospect.
“Gautam’s recent paper does the hard
biochemical and genomics work to
igure out how bacteria in the soil
degrade [one category of] antibiotics.”
The category Dantas chose to
analyze includes the
granddaddy of all
antibiotic drugs: penicillin.
Microbiologist Alexander
Fleming serendipitously
discovered it in 1928, and
variations on the original
are so abundant that it
remains the most common
class of antibiotic even
today.
The whole category is
based on a molecule called
beta-lactam, which is
naturally secreted by the
Penicillium chrysogenum
fungus, giving the species
a competitive advantage
against other microorganisms in the
wild. Beta-lactam works by weakening
the cell wall of the creature under
attack. But bacteria have evolved to
resist beta-lactam by producing an
enzyme that breaks the ringlike part of
its molecular structure.
Dantas set out to learn how some
soil microbes not only thwart the
toxin, but also thrive on it. He found
three distinct stages of antibiotic
catabolism (as the process of breaking
apart complex molecules is technically
known). First, the microbe cleaves
the beta-lactam ring in the same way
that most any resistant bug would do
it. Then it cuts off the broken ring
from the remainder of the penicillin
molecule, leaving behind a substance
called phenylacetic acid. In the inal
step, the bacteria swallow up the
phenylacetic acid as an energy source.
After determining which genes were
likely to give bacteria these abilities,
Dantas put them to the test by adding
them to the DNA of an unrelated
species, the bacterial workhorse E. coli.
When the E. coli was thus fortiied, it
ate its irst penicillin buffet.
ENGINEERING GLUTTONS
Recently, Dantas traveled to Peru to
sample sewage. He wanted to learn
how prevalent antibiotics were in
wastewater treatment plants, where
pathogens are also likely to be
present, and thus could be actively
evolving resistance. He found multiple
top-prescribed antibiotics in the
wastewater. Other studies have shown
high concentrations of penicillin and
other drugs in runoff from farms
and near pharmaceutical plants. If
these drugs could be eaten as rapidly
as they’re dumped, the pathogens
wouldn’t have a chance to get familiar
with them. A major cause of resistance
could be killed at the source.
Dantas believes that his transgenic
E. coli might just do the job, though
not the strain that his lab engineered,
which grows on penicillin very slowly
and prefers eating sugars. For this plan
to work, scientists will need to engineer
antibiotic gluttons.
Wright sees great
potential in the idea,
which could pre-treat
contaminated waste
products to remove
antibiotics even before
they get out into the open.
“The concentration of
antibiotics coming from
efuents of manufacturing
sites is stunning,” says
Wright. “Pre-treatment to
inactivate the compounds
would be of great beneit.”
Preemptive treatment could
also be helpful in hospitals,
eliminating antibiotics
before efuent ows into the municipal
sewage.
Unfortunately, the technique is
not risk-free. Researchers would
need different strains of these
microgourmands to disarm and
digest all relevant antibiotics, not just
penicillin. And there’s a danger in being
too successful. Bacteria are notorious
for sharing useful bits of DNA. The
drug-eating bacteria could seed the
next crop of antibiotic-resistant bugs.
“If it goes bad, we may never be able to
come back,” cautions Dantas.
One workaround would be to use
the transgenic bacteria as factories
for making enzymes that break down
antibiotics, and then releasing those
enzymes into the environment. (The
enzymes are not alive and don’t have GEOFF TOMPKINSON/SCIENCE SOURCE
Meanwhile,
scientists are
learning why
bacteria engage
in the seemingly
counterintuitive
behavior of eating
substances meant
to kill them.
Penicillium
chrysogenum
Prognosis