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Thursday, 28 July 2016 13:46

Deadly Superbugs Can Masquerade As Ordinary Bacteria

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The clinical microbiology
laboratory at Emory University
Hospital in Atlanta processes more
than 800 patient specimens every
day. Samples of urine or stool arrive
in stacks of petri dishes, sometimes
by pneumatic tube straight
from operating rooms. Most of the
microbes the lab's technicians investigate
are familiar creatures that
can be dealt with by modern medicine.
But in the fall of 2013, something
puzzling appeared.
Lab director Eileen Burd
and her staff of 36 work around the
clock to figure out what kind of infections
are making patients sick,
and what drugs will work best to
heal them. Three years ago, they
tested a strain of the bacteria E.
cloacae that infected a kidney
transplant patient. The bug fought
off a battery of antibiotics including
colistin, the drug doctors rely
on when no other antibiotics work.
Colistin killed most of the germs,
but a small colony survived.
This wasn't the first time a
resistant bug had been found. But
the fact the lab was even testing
colistin against the microbe "signaled
to me that this was a very resistant
organism to begin with,"
Burd said.
Discovered in 1949, colistin
was later abandoned in most
human medicine because of its
toxic side effects, but doctors have
been forced to employ it in recent
years to treat infections where most
other antibiotics fail.
For years scientists have
warned that humanity is squandering
antibiotics in medicine and
agriculture. The drugs are frequently
deployed against illnesses
they don't even treat, or to make
pigs, cows, and chickens grow
faster. Reckless practices can speed
the emergence of microbes that
can't be killed by any drug we
have. Cancer patients, premature
babies, and organ recipients all rely
on these medicines to fight off microbes
when their own immune
systems are weakened. Without effective
antibiotics, a skin infection
after a scraped knee could turn
Already, so-called superbugs
kill at least 23,000 people in
the U.S. every year and sicken 2
million. Globally, the number of
deaths annually is 700,000, but that
figure could spike to 10 million by
2050, according to a May report
commissioned by the British government.
That would make superbugs
bigger killers than cancer.
While these bacteria and
what they might do in 30 years are
scary, what's more frightening is
that some may have the biological
equivalent of stealth technology:
They appear to be treatable because
diagnostics aren't sensitive
enough to detect their resistance
powers. That's precisely what
Emory researchers found when
they began investigating the
strange organism that turned up in
that kidney transplant patient.
Burd sent the sample to a
colleague, microbiologist David
Weiss, at Emory’s School of Medicine.
“I called him and I said,
‘David, I think I’ve got something
weird,’” she said.
Weiss is an academic researcher
who can spend years untangling
the inner workings of a
single type of bacteria. Burd runs a
workhorse hospital lab that delivers
results to doctors in hours.
They live in different worlds, and
in many academic medical centers,
the two would never cross paths.
But a few years ago, Emory decided
that bringing the Burds and
Weisses of the world together
would be essential to tackling the
urgent problem of superbugs.
“The problem of antibiotic resistance
threatens our entire medical
system,” says Weiss, 39. “It’s only
going to get worse before it gets
Weiss traces his love of biology
to childhood trips with his
grandmother to the Central Park
Zoo, where his favorite animal was
the elephant. As he grew older, he
became fascinated with nature's
smallest life-forms. “How could it
be that these little primitive singlecelled
organisms could do all these
terrible things to us?” he asks.
Two years ago, he became
director of the new Emory Antibiotic
Resistance Center, which includes
a network of 35 faculty
members, a gaggle of students and
postdocs, and more than $10 million
a year in research grants. His
lab is hidden in the forest on the
edge of the university's campus, a
short drive from the busy hospital.
In the hallway outside the labs,
graduate students leave their water
bottles, thermoses, and half-eaten
slices of pizza on top of a small
fridge to avoid picking up
pathogens they're studying. Inside,
researchers conduct experiments
with some of the trickiest bacteria
there are.
The bugs evolve constantly,
and scientists don’t fully understand
all the ways they can defy
medicines. “These organisms, because
they replicate every 20 minutes
and there’s untold trillions of
them, are out ahead of us,” says
Cliff McDonald, associate director
for science at the Centers for Disease
Control’s division of healthcare
quality promotion.
Since the unwelcome surprise
inside that Emory transplant
patient, another troubling development
arose, this time in China. In
November, researchers there identified
a gene called MCR-1 that
makes microbes resistant to colistin.
MCR-1 wasn’t among the
thousands of resistance genes scientists
had already cataloged.
When health authorities around the
world went back and tested samples
in storage, they found the new
gene in at least 19 countries.
On May 27, as Americans
were preparing for the long Memorial
Day weekend, U.S. authorities
announced they had detected
MCR-1 in a Pennsylvania patient’s
urinary tract infection and, separately,
in a sample from a pig intestine.
The bacteria remained
susceptible to some other drugs,
just not colistin.
But the gene is particularly
scary because it can spread swiftly
to other types of bacteria, imbuing
new strains with resistance traits. If
it reaches a bug like CRE (carbapenem-
resistant enterobacteriaceae),
the highly resistant bacteria
that the head of the CDC has called
a "nightmare bacteria," resulting
infections could be untreatable.
Back at Emory, the type of
resistance uncovered in the kidney
transplant patient didn't generate
the same alarming headlines, in
part because it was a bug that can't
spread its resistance power as easily
to other types of bacteria. But their findings, published
in the journal Nature Microbiology
in May, raise a different
concern: that routine diagnostics
can miss superbugs, incorrectly labeling
them as susceptible to treatment.
The sample from the patient
turned out to have an unusual
form of resistance: A small population
of the bugs survived treatment
with colistin even though they
were genetically identical to ones
that were vulnerable to the drug.
More concerning still, the resistant
bacteria flourished in mice without
any treatment, actually reproducing
faster as a result of the rodents'
own immune response.
Victor Band, a fifth-year
graduate student in Weiss's lab,
said the small population of resistant
bacteria begins to expand when
the mouse's immune system tries to
fight the infection. Nature's chemical
defenses killed some of the
bugs but made the surviving ones
stronger. Colistin had the same effect.
"It’s almost like a stacked
deck against the drug," Weiss said.
How could doctors treat an infection
that behaves that way in a
human patient? "It’s a conundrum."
(Under medical privacy
rules, the fate of the original
human patient infected was not
After analyzing the initial
strain from Emory, Weiss’s lab got
several similar bugs from the
freezers of the Georgia Emerging
Infections Program, a collaboration
among Emory, the CDC, and the
state's health department. For 25
years, the program has been tracking
unusual or important pathogens
circulating in hospitals, the community,
and the food supply.
They found a similar strain
of E. cloacae with a small subpopulation
that colistin couldn’t kill.
But the standard lab tests indicated
that this strain was susceptible to
antibiotics. The superbug was masquerading
as a more vulnerable microbe.
To be sure, antibiotics still
remain effective most of the time.
But science has blind spots:
"We should be most concerned,
I think, about the problems
we don’t even know about,” Weiss
says. "Those are the ones that can
really creep up on you.”
It's hard to tell how often
antibiotics fail, but such cases
aren't unheard of. Even a bacterium
considered "susceptible" to a particular
drug may not respond to the
treatment up to 10 percent of the
time, though other medicines will
often still work. The kind of phenomenon
Weiss’s team identified
might explain mysterious treatment
They’re currently investigating
how prevalent such strains may
be through a network of other U.S.
The weird bug that Burd
flagged to Weiss could have easily
been shelved in another hospital.
To better understand what kind of
novel pathogens are circulating,
Emory plans to set up a new lab
capable of more closely examining
unusual specimens from hospital
The goal is to "not to lose
something that’s really interesting
and let it slip through our fingers,”
Weiss says.
The government is waking
up to the same need, albeit on a
broader scale. Stronger surveillance,
improved diagnostics, and
accelerated research are central elements
of the National Action Plan
for Combating Antibiotic-Resistant
Bacteria, published by the White
House in March 2015. That document,
just 15 months old, makes no
mention of colistin resistance, or
the MCR-1 gene. They weren’t on
the radar last year.
But the CDC is ramping up
to fight superbugs. Armed with
$160 million from Congress, the
agency plans to equip about eight
labs around the country to test resistant
bacteria discovered in hospitals
and clinics. They should start
operating in the fall. It’s also trying
to improve the capabilities of state
public health departments to track
superbugs. “We need to have a robust
system for seeing, understanding
what’s out there, in terms of
what’s making people sick," says
Beth Bell, director of the CDC’s
National Center for Emerging and
Zoonotic Infectious Diseases.
In the meantime, Emory’s
superbug hunters will continue to
search for strange organisms passing
through the hospital lab. “It
takes somebody recognizing that
something is odd,” Burd says, "and
then kind of knowing or figuring
out what to do with it."

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