May 8, 2000


WALNUT CREEK- A team of researchers has unraveled in one day'sworkload the entire genome of a harmful bacterium, dubbed the"superbug," that is a leading cause of hospital-acquiredinfections.

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

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

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

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

Work on the sequencing and the development of the bacterium's DNAlibraries was funded by the Department of Energy and the NationalInstitute 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 atthe 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) askedme if we could help him with their work on this pathogen, we leapt atthe chance to both demonstrate the capability and provide a usefulservice to the medical community. Merely for convenience, we spreadthe work over two consecutive days, but we used only one day ofcapacity to accomplish the task.

"I believe this kind of fast response capability could prove to bevery useful to researchers in medical, national security andagricultural contexts," Branscomb added.

Armed with the bacterium's full genome sequence, medicalresearchers can now work on finding the organism's vulnerabilitiesand picking which protein targets to direct vaccines against, saidWeinstock, the co-director of the Human Genome Sequencing Center atBaylor College of Medicine.

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

During the past 20 years, infections by E. faecium and otherenterococci have surged dramatically. Enterococci are now are secondmost common pathogen isolated from hospital-acquired infections inthe U.S., Weinstock said.

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

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

Hospital-acquired pathogens, such as E. faecium, have had greaterimpacts in industrialized nations like the U.S., especially inpatients with long hospital stays, on multiple antibiotics and with anumber of medical problems, such as cancer or prior surgery, saidBarbara Murray, co-director with Weinstock of the Center for theStudy of Emerging and Re-Emerging Pathogens at the University ofTexas Houston Medical School.

The recently-sequenced bacterium has the ability to spreadthroughout 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 intest tube studies that show promise against organisms such as E.faecium, Weinstock said.

"As a result, the study of fundamental properties of this organismis likely to play an important role in discovering new means totreat, prevent or modulate enterococcal infections," Weinstocksaid.

Future work at the JGI and the Baylor College of Medicine willcomplete the final assembly of the E. faecium genome and provide amore 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 January1999, it has increased its production rates by more than 20-fold toapproximately 25 million raw bases per day with an essentiallyconstant budget, Branscomb said.

More information about the JGI is available at its website:

Founded in 1952, Lawrence Livermore National Laboratory is amultidisciplinary, national security laboratory that applies scienceand technology to the significant issues of our time. The Laboratoryis managed by the University of California for the U.S. Department ofEnergy.