Genome analysis sheds light on drug-resistant pathogen

Mobile DNA’s role in vancomycin resistance of Enterococcus faecalis

‘Jumping’ elements of DNA have enabled the bacterium Enterococcus faecalis to acquire stubborn resistance to a range of antibiotics – including a “drug of last resort” that is used against such bacterial pathogens.

That is one of the conclusions reached by scientists at The Institute for Genomic Research (TIGR), which sequenced and analyzed the complete genome of E. faecalis V583, a strain of the opportunistic pathogen that is resistant to the antibiotic vancomycin. That strain was first isolated at a St. Louis hospital in 1987.

The results of this work, supported by the National Institute of Allergy and Infectious Diseases (NIAID), are published in a paper in this week’s issue of Science.

Ian Paulsen, Ph.D., the TIGR researcher who is the first author of the Science paper, says the genome analysis found that “mobile elements” – small segments of DNA that can jump between organisms or their chromosomes – appear to play an important role in helping the bacterium quickly develop drug resistance.

The TIGR analysis found that nearly a third of the E. faecalis genome – which encompasses more than 3.2 million DNA base pairs – consists of mobile or ‘foreign’ DNA “That’s an unusually high percentage of mobile elements in a microbial genome,” said Paulsen.

Those mobile elements include three plasmids in the bacterium and multiple remnants of phage, plasmids, and other mobile elements, including transposons and a pathogenicity island located on its single chromosome. Scientists identified two sites in the genome that are related to vancomycin resistance or tolerance.

One of those sites, Paulsen said, appears to be a newly-identified vancomycin resistance transposon, carrying vanB resistance genes. A transposon is a mobile element that can “jump” from one part of a chromosome to another, or from a chromosome in one organism to that of another organism – sometimes carrying along genes that encode for drug-resistance. In the case of vanB, the encoded genes allow the bacterium to alter its cell wall structure to prevent vancomycin from damaging it.

“It’s clear that Enterococcus’s ability to acquire mobile elements has significantly contributed to its drug resistance,” says Paulsen. “The vancomycin resistance is found on a mobile element in the genome.”

TIGR’s president and director, Claire M. Fraser, Ph.D., says the deciphered Enterococcus genome will provide an important tool for biomedical researchers. “The identification of a novel vancomycin-resistant transposon in E. faecalis demonstrates the power of genomics to reveal new insights into the biology of important human pathogens,” Fraser says. “This information is critically important in the search for new antibiotics and vaccines to combat infections diseases.”

E. faecalis lives in the gastrointestinal tracts of humans and animals and is often found in soil, sewage, water and food as a result of fecal contamination. While the bacterium is normally symbiotic in the human gut – causing no harm – it can cause serious infections when other tissues are exposed to the bacterium. Those maladies include infective endocarditis, bacteremia, and urinary tract infections.

Physicians often use vancomycin to treat opportunistic E. faecalis infections if other drugs fail to slow their progress. But the growing number of bacterial strains that are resistant to such antibiotics has made it more difficult for physicians to treat those infections effectively.

An even greater concern is that E. faecalis has been found to act as a “reservoir” for vancomycin resistance. Other researchers already have observed how resistance to vancomycin can be transferred from E. faecalis to more aggresively pathogenic bacteria such as Staphylococcus aureus. That transferral of drug resistance has become a major concern for physicians around the globe.

The Institute for Genomic Research (TIGR) is a not-for-profit research institute based in Rockville, Maryland. TIGR, which sequenced the first complete genome of a free-living organism in 1995, has been at the forefront of the genomic revolution since the institute was founded in 1992 and is a leading center for microbial genomics. TIGR conducts research involving the structural, functional, and comparative analysis of genomes and gene products in viruses, bacteria, archaea, and eukaryotes.

Additional Contact:
Ian Paulsen, Ph.D., Assistant Investigator, TIGR
(301) 838-3531 or ipaulsen@tigr.org