Epidemic of Escherichia coli infections traced to one strain of bacteria

Fast-evolving lethal clone spreads worldwide, according to new study published today

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 44 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.

Riddell and TGen Welcome Arizona State University Football Program as First-Ever Collegiate Partner in Genetic Study of Concussion Detection, Treatment

ROSEMONT, Ill. and TEMPE, Ariz., Sept. 12, 2013 /PRNewswire/ — Riddell, the leader in football helmet technology and innovation, today announced that the Pac-12’s Arizona State University and its Sun Devil football program will participate as the first university research partner in a new study designed to advance athlete concussion detection and treatment. This potentially groundbreaking joint research project is the first of its kind to combine molecular information with the monitoring of head impacts.

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Working with the Translational Genomics Research Institute (TGen) and its research partners, the Sun Devil football team will participate in the study to identify whether the effects of sub-concussive hits are identifiable through blood-based molecular information. The researchers will monitor the players’ changing molecular information throughout a season of typical head impact exposure associated with football practice and games.

The Riddell Sideline Response System (SRS) has been deployed for use at Arizona State University for the 2013 college football season to obtain real-time head impact data from Sun Devil football players.  Information gathered from the system will be combined with molecular information from players that experience concussion, with the objective of helping physicians diagnose concussion and better identify when a player might be expected to recover and return to the field. TGen and Riddell announced their research collaboration in May.

Today’s football is played with ever-increasing levels of speed, strength and overall performance, with an unrelenting demand for cutting-edge protection to match.  Elite players turn to Riddell for its advanced equipment that allows for the highest level of performance, while providing that same level of protection when it matters most – on game day.

“Our goal is to be leaders in the community, on and off the field, and partnering with industry pioneers like Riddell and TGen enables us to be proactive in helping to advance the game and enrich the lives of our student-athletes,” said Steve Patterson, Vice President for Sun Devil Athletics. “Involvement in this study is consistent with our long-term goals, and also increases awareness and understanding of this important topic, as well as furthers the Pac-12’s Student-Athlete Health and Well-Being Initiative.”

The Sun Devils’ medical team, consisting of athletic trainers and physicians, will not see the data or interpret any results until the end of the season, and the student-athletes wearing the Riddell SRS sensors in their helmets volunteered to partake in the study.

At the heart of the study is merging a player’s molecular information with real-time head impact information captured by Riddell’s exclusive SRS technology. Riddell, in partnership with Simbex, LLC, was the first to introduce a helmet-based player monitoring and response system to the sport of football. The data output provides researchers, athletic staff and players with a wide range of valuable information – transmitted directly to the sidelines via wireless communication – on the frequency and severity of head impacts a player receives during games and practices. Riddell SRS has captured over 1.8 million impacts from youth to elite football competition since instituted in 2003 by several well-respected research institutions, leading to important rule changes and informing new helmet designs.

With the high expectations for the Sun Devil football team this year, Arizona State’s implementation of Riddell SRS reinforces the school’s commitment to their student athletes’ well-being and helps to ensure they’re performing at the optimal level.

“Together with Arizona State University, TGen and our other important research partners, we at Riddell hope to answer a number of key questions that will lead to improved player protection, inform our continued development of new helmet innovations and further refine player monitoring technology,” said Dan Arment, President of Riddell.

Among those questions is whether the effects of sub-concussive hits are identifiable through blood-based molecular information that could unlock new opportunities for innovation and advancement of the game. Researchers at TGen, along with their colleagues, hope to find the answers in the data.

During this phase of the study, TGen faculty and staff have been on the sidelines working closely with their colleagues at Barrow Neurological Institute, A.T. Still University and Desert Testing collecting samples and data.

A baseline sample was collected from all participating players prior to their pre-season workouts. Since then, the researchers have followed the team through their daily workouts and will continue throughout the season, securing samples the day after each practice or game. Through the collection of samples over various points in time and the data generated by Riddell SRS, the goal is to identify the genomic changes in athletes exposed to routine head impacts during practice and games, athletes with diagnosed concussions that recover on both a routine time scale, and athletes with persistent symptoms following concussion that require additional treatment.

“There is no time to waste in bridging the information gathered through Riddell SRS and the genomic information we will gather to hopefully glean a clearer picture of how concussions impact human neurological function in terms of injury, recovery and future risk for long term complications. We are indeed excited to join the ASU football program and Riddell in this pioneering study,” said Dr. Jeffrey Trent, TGen President and Research Director.

Following the season long campaign, the researchers will gather post-season baseline data and begin the analysis process with their colleagues at Barrow Neurological Institute and A.T. Still University. During this process, TGen will work closely with Barrow, whose B.R.A.I.N.S. (Barrow Resource for Acquired Injury to the Nervous System) program treats patients who have sustained a traumatic brain or spinal cord injury. The Barrow data will provide the researchers with additional concussion data and allow for comparison between data sets.

About Riddell
Founded in 1929, Riddell is a premier designer and developer of protective sports equipment and a recognized leader in helmet technology and innovation. One of Easton-Bell Sports Inc.’s most well-known brands and the Official Helmet of the NFL®, Riddell is the leading manufacturer of football helmets, shoulder pads and reconditioning services (cleaning, repairing, repainting and recertifying existing equipment). For more information, visit our website at www.riddell.com, like the Riddell Facebook page, or follow Riddell on Twitter @RiddellSports.

About Arizona State University
Arizona State University is one of the top 100 research universities in the world and fifth in the United States for producing career-ready graduates with the skills to succeed in the workforce. It is the largest public research university in the nation under a single administration, with total student enrollment of more than 76,000 in metropolitan Phoenix, the nation’s fifth-largest city. ASU is creating a new model for American higher education, an unprecedented combination of academic excellence, entrepreneurial energy and broad access.  This New American University is a single, unified institution comprising four differentiated campuses positively impacting the economic, social, cultural and environmental health of the communities it serves.  Its research is inspired by real world application, blurring the boundaries that traditionally separate academic disciplines.  ASU champions intellectual and cultural diversity, and welcomes students from all fifty states and more than one hundred nations across the globe.

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 neurological disorders, cancer, 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 world-wide, TGen makes a substantial contribution to help our patients through efficiency and effectiveness of the translational process. For more information, visit: www.tgen.org.

About Barrow Neurological Institute
Barrow Neurological Institute at St. Joseph’s Hospital and Medical Center is an internationally renowned medical center that offers care for people from throughout the world with brain and spine diseases, disorders and injuries. Barrow performs more neurosurgeries annually than any hospital in the United States. U.S. News & World Report routinely lists St. Joseph’s among the best hospitals in the nation for neurological and neurosurgical care.

About AT Still University
Established in 1892 by A.T. Still, MD, DO, the founder of osteopathy, A.T. Still University began as the nation’s first college of osteopathic medicine and has evolved into a leading university of health sciences comprised of one college and four schools on two campuses and online. Today we offer master’s degrees across allied health disciplines; doctorates in health education, physical therapy, health sciences, and audiology; the doctor of dental medicine; and the doctor of osteopathic medicine.

 

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