Research breakthrough heralded as key insight that can lead to more accurate clinical laboratory tests and more effective antibiotics for treating E. Coli infections

Antibiotic-resistant strains of bacteria are one of healthcare’s biggest threats to patient safety and improved patient outcomes. Now advanced gene sequencing has given researchers a startling new understanding of how Escherichia coli (E. coli) has developed resistance to antibiotics.

This discovery may have a major impact on microbiology labs in hospitals, because they do so much of the medical laboratory testing to detect and identify infections. These new research findings also demonstrate to pathologists how quickly genome analysis can generate new knowledge about diseases and their causes.

Single Strain of E. coli Responsible for Most Resistance to Antibiotics

Researchers who conducted a new study of E. coli were shocked to discover that a lethal, antibiotic-resistant clone of the bacteria derives from a single strain. This is significant because E. coli infection has become a worldwide epidemic.

Scientists had assumed that the fast-evolving strain of E. coli had gained resistance to antibiotics through separate genetic events in different parts of the world. This new insight into the monoclonal source of the superbug could lead to development of new preventative techniques, diagnostic tests and therapeutic drugs.

Knowledge of a Single Enemy

“We now know that we are dealing with a single enemy,” stated Evgeni V. Sokurenko, M.D., Ph.D., Professor of Microbiology, University of Washington in a press release published at eurekalert.com. “[B]y focusing on this super-clone we can have a substantial impact on this worldwide epidemic,”  he said.

Pictured is one of the three lead investigators that researched antibiotic resistance of E. coli, Evgeni V. Sokurenko, M.D., Ph.D., Professor of Microbiology at the University of Washington. He and his colleagues determined that a single strain of E. coli is responsible for most resistance to antibiotics. The team’s findings may lead to new medical laboratory tests that can more accurately detect this strain of E. coli. (Photo copyright by the University of Washington.)

Pictured is one of the three lead investigators that researched antibiotic resistance of E. coli, Evgeni V. Sokurenko, M.D., Ph.D., Professor of Microbiology at the University of Washington. He and his colleagues determined that a single strain of E. coli is responsible for most resistance to antibiotics. The team’s findings may lead to new medical laboratory tests that can more accurately detect this strain of E. coli. (Photo copyright by the University of Washington.)

 

Sokurenko is one of three lead investigators on the international collaborative study team. The others are James R. Johnson, M.D., and Lance Price, Ph. D.. Dr. Johnson is Professor of Medicine at the University of Minnesota and the University of Minnesota Veterans Affairs Medical Center. Dr. Price is a professor in the Department of Environmental and Occupational Health at George Washington University School of Public Health and Health Services and Associate Professor in the Pathogen Genomics Division of the Translational Genomics Research Institute of Arizona. Researchers at Group Health Clinical Laboratory and the Group Health Research Institute in Seattle also participated in the study.

Virulent, Drug-resistant E. Coli Is a Major Public Health Threat

In the past decade, a single E. coli clonal group, ST131, has become the main cause of bacterial infections in women and the elderly, according to the new study published in the December 17 issue of mBio. mBio is an open access journal published by the American Society for Microbiology.

ST131 bacteria invade the bladder and kidneys. They have also become adept at moving from the kidneys into the bloodstream. In the United States alone, urinary tract infections (UTI) affect more than 10 million people annually, according to the press release. The ST131 strain may be responsible for 1.5 million of those UTIs and tens of thousands of deaths in the U.S. each year.

The findings of a 2010 study established ST131 as a major drug-resistant pathogen in the United States and an important new public health threat. “The clinical and public health implications of the… high prevalence of ST131… are potentially profound,” declared Dr. Johnson, who was lead investigator on the earlier study.

Evolution of a Killer Clone with Unprecedented Social Impact

Over a decade ago, the ST131 E. coli strain gained mutations in two genes, the press release reported. This gave rise to the H30-R clone. The H30-R clone became fully resistant to the then-wonder drug Cipro (ciprofloxacin), a second-generation fluoroquinolone.

Shortly thereafter, a new clone evolved from H30-R called H30-Rx. H30-Rx is resistant to several extended-spectrum antibiotics. These include third-generation cephalosporins. “This strain of E. coli spreads from person to person and seems to be particularly virulent,” stated Johnson in the release.

“In some hospitals it is responsible for up to half of E. coli infections,” declared Sokurenko in a story posted on the University of Washington website. The strain is fast growing and can spread from person to person. It is particularly adept at invading the bloodstream.

“It is the most common single strain causing sepsis, a deadly form of blood infection that kills 20% to 40% of patients who develop it,” continued Sokurenko. “Due to its wide-spread resistance and virulence, the social and economic impact of H30-Rx clone could exceed that of any other bacterial strain known.”

Researchers Use Whole-genome Sequencing and Phylogenomics

Researchers collected scores of ST131 bacterial samples from patients and animals in five countries that dated from 1967 to 2011, the press release reported. They used a technique called whole-genome-sequence-based phylogenomics to analyze the samples. This allowed them to construct a family tree that revealed the bacteria’s evolutionary history.

“Astoundingly, we found that all of the resistance could be traced back to a single ancestor,” stated Dr. Price in the release. The results showed that almost all ST131 strains responsible for the notoriously resistant infections are very closely related to each other.”

The researchers hope the study’s findings will make it possible to develop better tools to identify, stop or prevent the spread of the ST131 strain, according to Johnson. The results could help to find better ways to block the transmission of the superbug and in developing a vaccine.

Developing New Diagnostic Tests for Clinical Laboratories

Further, these new scientific findings may lead to the development of diagnostic tests that would help physicians to make faster, more accurate identification of infections. That would help pathologists and clinical laboratory scientists provide more value with medical laboratory tests that improve patient outcomes and reduce deaths from infections.

—Pamela Scherer McLeod

Related Information:

The Epidemic of Extended-Spectrum-β-Lactamase-Producing Escherichia coli ST131 Is Driven by a Single Highly Pathogenic Subclone, H30-Rx

Escherichia coli sequence type ST131 as the major cause of serious multidrug-resistant E. coli infections in the United States

Epidemic of Escherichia coli infections traced to 1 strain of bacteria

E. Coli ‘Superbug’ May Pose Major Health Threat: Study

Epidemic of escherichia coli infections traced to one strain of bacteria

‘Particularly Virulent’ Strain Of E. Coli ‘Superbug’ Implicated In Lethal Urinary Tract Infections