2013-12-17

FLAGSTAFF, Ariz., and WASHINGTON, D.C. - Dec. 17, 2013
- In the past decade, a single strain of Escherichia
coli, or E. coli, has become the main cause of
bacterial infections in women and the elderly by invading the
bladder and kidneys, according to a study published today in the
American Society for Microbiology's open access journal
mBio.

Besides becoming more resistant to antibiotics, the strain
H30-Rx gained an unprecedented ability to spread from the
urinary tract to the blood, leading to the most lethal form of
bacterial infections - sepsis - and posing a looming threat to the
more than 10 million Americans who annually suffer from urinary
tract infections (UTIs).

 

This new study could help trace the evolutionary history of this
superbug and possibly lead to the development of a vaccine,
according to Lance B. Price, Ph.D., the study's lead author. 
Price is professor of environmental and occupational health at the
George Washington University School of Public Health and Health
Services (SPHHS), and is an associate professor in the Pathogen
Genomics Division of the Translational Genomics Research Institute
(TGen).

Previous research suggested that the ST131 group of E.
coli - a family of many genetically related strains of
bacteria - had independently gained resistance to antibiotics
through separate genetic events. The ST131 group had been
identified as a major source of superbugs - microbes resistant to
multiple antibiotics - among UTI bacteria. If true, the existence
of many different resilient strains would prove a formidable threat
with multiple ways of evading the immune system and medical
treatment, according to the new study.

Using advanced genomic techniques, Price and collaborators - James
R. Johnson of the Veterans Affairs Medical Center and the
University of Minnesota, and Evgeni V. Sokurenko of the University
of Washington School of Medicine - discovered that the ST131
strains represented genetic clones abruptly evolved from a single
strain of E. coli.

By gaining mutations in two genes, a strain called H30
gave rise more than a decade ago to the H30-R clone, which
became fully resistant to the then-wonder-drug known as
Cipro.  Soon after, a new clone evolved from H30-R
called H30-Rx, which is resistant to several
extended-spectrum antibiotics, such as third-generation
cephalosporins.

Using whole-genome sequencing - spelling out, in order, each
molecule of DNA - researchers analyzed the genomes of E.
coli samples from patients and animals in five countries over
48 years, 1967-2011. They created a family tree tracing how the
superbug clones emerged as the result of discrete genetic
events.

"Astoundingly, we found that all of the resistance could be traced
back to a single ancestor," Price said. "Our research shows this
superbug then took off, and now causes lots of drug-resistant
infections."

H30-Rx, appears to be much more adept than other E.
coli at ascending from the bladder to the kidneys and then
into the bloodstream, where it can be lethal, and the study
suggests that H30-Rx may be responsible for 1.5 million
UTIs and tens of thousands of deaths annually in the United
States.

This study shows that, by focusing on H30-Rx, researchers
might find a vaccine that could prevent many infections. 
Vaccines for highly resistant strains of superbugs could protect
people from ever getting sick in the first place, Price said.

"This strain of E. coli spreads from person to person and
seems to be particularly virulent," Johnson said. "This study might
help us develop better tools to identify, stop or prevent its
spread by finding better ways to block the transmission of the
superbug, or by finding a diagnostic test that would help doctors
identify such an infection early on - before it might have the
chance to turn lethal."

Sokurenko added, "We now know that we are dealing with a single
enemy, and that by focusing on this strain we can have a
substantial impact on this worldwide epidemic."

The study, The epidemic of ESBL-producing Escherichia coli
ST131 is driven by a single highly pathogenic subclone,
H30-Rx, appears today in the peer-reviewed online-only
scientific magazine mBio - the flagship journal of the
American Society for Microbiology and the American Academy of
Microbiology.

# # #

About the George Washington University School of Public
Health and Health Services:

Established in July 1997, the School of Public Health and Health
Services brought together three longstanding university programs in
the schools of medicine, business, and education and is now the
only school of public health in the nation's capital. Today, more
than 1,100 students from nearly every U.S. state and more than 40
nations pursue undergraduate, graduate, and doctoral-level degrees
in public health.  The school now offers an online Master of
Public Health, MPH@GW, which allows students to pursue their degree
from anywhere in the world. http://sphhs.gwu.edu/

Press Contact:
Kathy Fackelmann

George Washington University

202-994-8354
kfackelmann@gwu.edu

About TGen:

Translational Genomics Research Institute (TGen) is a Phoenix,
Arizona-based non-profit organization dedicated to conducting
groundbreaking research with life changing results. TGen is focused
on helping patients with cancer, neurological disorders and
diabetes, through cutting edge translational research (the process
of rapidly moving research towards patient benefit).  TGen
physicians and scientists work to unravel the genetic components of
both common and rare complex diseases in adults and children.
Working with collaborators in the scientific and medical
communities literally worldwide, TGen makes a substantial
contribution to help our patients through efficiency and
effectiveness of the translational process. For more information,
visit: www.tgen.org.

Press Contact:

Steve Yozwiak

TGen Senior Science Writer

602-343-8704
syozwiak@tgen.org

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