December 17, 2013

Epidemic of E. coli infections traced to one strain

Fast-evolving lethal clone has spread around the world, according to new study

Seattle, WA—Virulent, drug-resistant forms of Escherichia coli that have recently spread around the world emerged from a single strain of the bacteria—not many different strains, as has been widely supposed, according to a new study in mBio, the flagship journal of the American Society for Microbiology.

The strain causes millions of urinary, kidney, and bloodstream infections a year and has a far greater clinical and economic impact than any other strain of bacteria, including the so-called MRSA (methicillin-resistant Staphylococcus aureus) superbug.”

The research on drug-resistant E. coli was conducted by an international collaborative research team that included Evgeni V. Sokurenko, MD, PhD, a professor of microbiology at the University of Washington, as well as Delia Scholes, PhD, a senior investigator at Group Health Research Institute and Kim Riddell, MD, medical director of Group Health’s Clinical Laboratories.

Unlike previously identified superbugs that are usually from multiple strains, these E. coli bacteria belong to just one closely related clone.

“We now know that we are dealing with a single enemy, and that by focusing on this super-clone we can have a substantial impact on this worldwide epidemic,” Dr. Sokurenko said.

Over the past decade, public health officials noted that E. coli belonging to the ST131 strains family emerged as a major cause of urinary tract and kidney infections. These are the most common bacterial infection in women and elderly. The ST131 bacteria were notable because they had acquired resistance to a class of relatively new antibiotics called fluoroquinolones, which were commonly used to treat urinary tract infections. More recently, these pathogens also acquired genes for extended-spectrum beta-lactamase.

This change rendered a broad spectrum of antibiotics, including highly potent penicillin derivatives and cephalosporins, ineffective against these strains of bacteria. As a result, the infections are increasingly difficult to treat.

These various resistant strains were assumed to have emerged independently around the world in response to their exposure to antibiotics. But this was proven to be incorrect by the laboratories of Sokurenko and two other lead investigators on the study: Lance B. Price, PhD, a professor of environmental and occupational health at the George Washington University School of Public Health and Health Services and an associate professor in the Pathogen Genomics Division of the Translational Genomics Research Institute in Arizona, and James R. Johnson, MD, a professor of medicine at the Veterans Affairs Medical Center and the University of Minnesota.

In the new study, researchers sequenced the genomes of scores of ST131 bacterial samples collected from patients and animals around the world. Then, using a technique called whole-genome-sequence-based phylogenomic analysis, the researchers constructed a family tree that revealed the bacteria’s evolutionary history.

That analysis indicated that almost all ST131 strains responsible for the notoriously resistant infections are very closely related to each other. They arise from a single clone that is termed H30-Rx for its resistance to treatment.

“Astoundingly, we found that all of the resistance could be traced back to a single ancestor,” said Dr. Price. “This superbug then took off, and now causes lots of drug-resistant infections.” In addition, the H30-Rx strain is fast-growing and can spread from person to person. It infects both the healthy and infirm, young and old, and is adept at invading the bloodstream, said Sokurenko.

“In some hospitals it is responsible for up to half of E. coli infections. It is the most common single strain causing sepsis, a deadly form of blood infection that kills 20 percent to 40 percent of patients who develop it,” he said. “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.”

According to Dr. Johnson, the study’s findings may make it possible to 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.”

In addition to the United States team, researchers from the Universitatsklinikum Munster in Muenster, Germany and the Statens Serum Institute in Copenhagen, Denmark participated in the study.

The research was supported by Office of Research and Development, Medical Research Service, Department of Veterans Affairs, Merit Review grant # 1 I01 CX000192 01488; the TGen Foundation; NIH grant RC4 AI092828; and USAMRMC grant W81XWH-10-1-0753.

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