Researchers Unravel Genome For "Superbug" Bacterium Using One Day's Production Capacity

The effort completed the first phase of genome sequencing (the shotgun sequencing phase) to a level sufficient to permit essentially all of the organism's genes to be identified.

The genome for Enterococcus faecium, known as the superbug because of its resistance to antibiotic treatments, was sequenced at the Department of Energy's Joint Genome Institute (JGI) in Walnut Creek, Ca.

The project was a collaboration between the JGI, led by Elbert Branscomb and Trevor Hawkins, and George Weinstock and Barbara Murray of the University of Texas Health Science Center and Baylor College of Medicine in Houston.

"This is an excellent demonstration of the technological prowess of the Department of Energy's Joint Genome Institute," said Energy Secretary Bill Richardson. "This new capability to rapidly decode the DNA of microbes can be used to provide the scientific community with a huge amount of fundamental data about life and the microbial world. This information allows us to explore bacteria that cause disease, as well as bacteria that can clean up the environment and benefit us in many other ways."

Work on the sequencing and the development of the bacterium's DNA libraries was funded by the Department of Energy and the National Institute of Allergy and Infectious Diseases.

The 2.8 million base pairs of DNA that make up the genome of E. faecium were sequenced using a single day's production capacity at the JGI's Sequencing Facility.

"I've been saying that, 'We could sequence a bacterium in a day,'" said JGI Director Elbert Branscomb. "So when George (Weinstock) asked me if we could help him with their work on this pathogen, we leapt at the chance to both demonstrate the capability and provide a useful service to the medical community. Merely for convenience, we spread the work over two consecutive days, but we used only one day of capacity to accomplish the task.

"I believe this kind of fast response capability could prove to be very useful to researchers in medical, national security and agricultural contexts," Branscomb added.

Armed with the bacterium's full genome sequence, medical researchers can now work on finding the organism's vulnerabilities and picking which protein targets to direct vaccines against, said Weinstock, the co-director of the Human Genome Sequencing Center at Baylor College of Medicine.

"This research breakthrough paves the way for preventive vaccines, in addition to better diagnostic tests and treatments," Weinstock noted.

During the past 20 years, infections by E. faecium and other enterococci have surged dramatically. Enterococci are now are second most common pathogen isolated from hospital-acquired infections in the U.S., Weinstock said.

Recently, there has been an escalating resistance by E. faecium to the antibiotic vancomycin, usually considered the last buffer of treatment, as well as to a number of other agents.

"The increase in resistance is a grave signal of the reduced effectiveness of antibiotics," Weinstock said.

Hospital-acquired pathogens, such as E. faecium, have had greater impacts in industrialized nations like the U.S., especially in patients with long hospital stays, on multiple antibiotics and with a number of medical problems, such as cancer or prior surgery, said Barbara Murray, co-director with Weinstock of the Center for the Study of Emerging and Re-Emerging Pathogens at the University of Texas Houston Medical School.

The recently-sequenced bacterium has the ability to spread throughout the body and can cause serious infections in the blood, heart, urinary tract, central nervous system and in wounds.

To date, only a few new antibiotic agents have been identified in test tube studies that show promise against organisms such as E. faecium, Weinstock said.

"As a result, the study of fundamental properties of this organism is likely to play an important role in discovering new means to treat, prevent or modulate enterococcal infections," Weinstock said.

Future work at the JGI and the Baylor College of Medicine will complete the final assembly of the E. faecium genome and provide a more complete analysis of its genetic structure.

The Joint Genome Institute was established in January 1997, merging the pre-existing genome programs of Lawrence Berkeley, Lawrence Livermore and Los Alamos national laboratories.

Since the JGI assumed occupancy of its new facility in January 1999, it has increased its production rates by more than 20-fold to approximately 25 million raw bases per day with an essentially constant budget, Branscomb said.

More information about the JGI is available at its website: http://www.jgi.doe.gov/

Founded in 1952, Lawrence Livermore National Laboratory is a multidisciplinary, national security laboratory that applies science and technology to the significant issues of our time. The Laboratory is managed by the University of California for the U.S. Department of Energy.