Team Genetically Maps Lethal Strains of E. coli

Scientists at the University of Maryland, School of Medicine (UM SOM) say they have for the first time determined the genetic makeup of various strains of E. coli, which every year kill hundreds of thousands of people around the world. Their paper, which appears in a recent issue of Nature Microbiology, analyzed the DNA of enteropathogenic Escherichia coli (EPEC), which are the bacterial strains that cause diarrhea.

    The team, led by David Rasko, Ph.D., associate professor of microbiology and immunology at the Institute for Genome Sciences (IGS) at UM SOM and Michael Donnenberg, M.D., professor of medicine at UM SOM, identified certain strains that are typically much more lethal than others. The results should help researchers focus efforts to identify, treat, and potentially control these more-dangerous versions. This could lead to a better understanding of exactly how the bacteria cause damage and, eventually, more-effective treatments that could significantly lower the death rate for diarrheal diseases, which are a leading cause of child mortality around the world. Each year diarrhea kills around 760,000 children under the age of five. It is also a leading cause of malnutrition in children under five years old. Globally, there are nearly 1.7 billion cases of diarrheal disease every year.

    “These findings really help us map the associations between the bacteria and these illnesses in a new way. This kind of research would not have been possible a few years ago,” says Dr. Rasko. “But with new advances, we can make these kinds of exciting discoveries.” He describes the research as “genomic epidemiology,” a new way of doing public health science that integrates the most cutting-edge technologies with an extensive knowledge of pathogenic bacteria, both of which exist at the University of Maryland, School of Medicine.

    Dr. Rasko and his colleagues examined the genomes of 70 strains of E. coli, which were obtained from infected children enrolled in the Global Enterics Multi-Center study (GEMS). Some of the cases were associated with death, other cases had symptoms but no death, and others were not associated with symptoms; as a result, the scientists had access to strains with a range of outcomes.

    They analyzed the genetic differences between the strains and mapped them onto disease outcome. Then, they divided the strains into categories based on genetic content and clinical outcome. They are not sure how the genetic variations may be linked to symptoms and outcomes, but the pattern provides a rich area for further research, says Dr. Rasko. He suspects that increased E. coli lethality is caused by a group of genes interacting rather than one or two genes.

    “This research epitomizes what IGS is all about,” noted Claire M. Fraser, Ph.D., director of IGS “We want to take genomics and use it in novel ways, ways that can be of practical use to clinicians around the world.”