2018-12-01_Discover

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