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| Mobile DNA: Genomic Studies Illuminate Antibiotic Resistance | ||||||||
| By Kate Dalke
April 4, 2003  |
In September 2002, a patient with a chronic foot ulcer checked into a Pennsylvania hospital. Doctors later discovered that the ulcer contained Staphylococcus aureus bacteria, one of the most common causes of hospital infections. The bacteria were resistant to vancomycin, the antibiotic of last-resort in fighting infections. It was only the second case of vancomycin-resistant staph reported in the United States. The Pennsylvania physicians also had evidence the bacteria had acquired these resistance genes from another species of bacteria often found in hospitals, Enterococcus faecalis. Antibiotic resistance is a frightening reality. Now, scientists are a step closer to understanding how antibiotic resistance spreads in the microbial world because the genomes of two gut bacteria have been sequenced. The microbes, which usually live harmlessly in our intestines, are Bacteriodes thetaiotaomicron and Enterococcus faecalis. Their genomes contain an incredible amount of mobile elements—DNA that can move around on chromosomes, among organisms and even between species. Mobile DNA can carry genes for virulence and drug resistance, as well as benign genes.
“These mobile elements give bacteria the ability to quickly pass on traits,” says Ian T. Paulsen, who led the enterococcus genome-sequencing project at the Institute for Genomic Research (TIGR) in Rockville, Maryland. Until sequencing the entire genome, scientists did not realize that a quarter of enterococcus’ genome is made-up of mobile DNA. In fact, its genome contains one of the highest percentages of mobile elements ever seen in bacteria. Within these regions are genes for vancomycin resistance and for virulence. It had long been established that enterococcus has mobile elements, says Gary M. Dunny of the University of Minnesota in Minneapolis, who studies the bacterium. “But until now, we have never had a picture of the entire genome of one strain and the total number of mobile elements, which is remarkably high,” he says. TIGR sequenced a strain from a patient with the first case of vancomycin-resistant E. faecalis in the United States. Bacteriodes is also rich in mobile elements, although these do not harbor antibiotic resistance genes. Jeffrey I. Gordon of Washington University School of Medicine in St. Louis, Missouri, led the bacteriodes project. “Bacteriodes is not carrying these genes now, but they can pick them up,” says Abigail A. Salyers of the University of Illinois in Urbana-Champaign. Salyers has also served as president of the American Society of Microbiology. “There is much greater potential for transferring resistance genes than we thought,” she adds. The genomes of bacteriodes and enterococcus reinforce something scientists have been concerned about for years: the remarkable fluidity of the bacterial gene pool. This fluidity allows bacteria to exchange DNA to enhance their ability to cause disease or their resistance to antibiotics. “It’s really becoming a problem now because we’re running out of antibiotics,” says Michael S. Gilmore of the University of Oklahoma in Oklahoma City. Gilmore studies enterococcus, and wrote a commentary accompanying the two papers in Science.
Bacteriodes, enterococcus and staph are just a few examples of bugs that are becoming increasingly difficult to treat. The widespread use of antibiotics puts selective pressure on only the hardiest bacteria to survive—which often carry virulence or drug resistance genes. “We’re facing something we’ve never faced before—the loss of a cure,” says Salyers. New antibiotics are expensive and difficult to develop and “pharmaceutical companies are shutting down antibiotic programs,” she adds. Hospitals are breeding grounds for some of these dangerous microbes. When you enter a hospital, your intestines carry a normal consortium of microbes. But taking antibiotics can kill susceptible bacteria and leave room for resistant enterococci to take up residence. These bacteria are lurking on medical instruments and surfaces—just waiting to be ingested and find a niche in your body. The drug-resistant, opportunist enterococci are then poised to infect other parts of the body like surgery wounds, the urinary tract and bloodstream. The gut environment also contributes to the spread of dangerous genes because enterococcus and bacteriodes live along with over 500 species of bacteria. In fact, there are more bacteria in our intestine than cells in our body. These gut bacteria are in contact with one another and with other bacteria that pass through the intestine, where they can swap virulence and resistance genes. “Your colon is a like a singles bar,” says Salyers. “Bacteria are passing DNA around like there’s no tomorrow.” These bacteria don’t just stay in your body, but pass into the water, soil and food supply we all share.
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