Research Focuses on Antibiotic-resistant Bacterium and Touches on Longevity

HOUSTON -- With the help of a tiny roundworm, microbiologist Danielle Garsin searches for weak spots in a tenacious bacterium that thwarts antibiotic attack while threatening hospital patients. Her research, which has uncovered a tantalizing potential connection between longevity and resistance to infection, earned Garsin one of only 12 grants awarded in 2004 under the Ellison Foundation New Scholars Program in Global Infectious Diseases.

The assistant professor in the medical school department of microbiology and molecular genetics will receive $50,000 a year for four years to continue her work on Enterococcus faecalis and the roundworm C. elegans.

E. faecalis is the second or third most common cause of infections that patients contract in hospitals, Garsin said. It causes bacteremia (blood infection), urinary tract infections and endocarditis (heart infection) and many strains carry resistance to antibiotics.

The bacterium employs several methods for sharing DNA, which is how it acquires and spreads traits such as antibiotic resistance. Recently, cases of enterococci spreading vancomycin resistance to other bacteria have been documented. As vancomycin is one of the last antibiotics available to treat infections resistant to everything else, this is of great concern.

By feeding E. facaelis to C. elegans, Garsin works to characterize disease-causing factors in the bacterium and understand genetic pathways of the worms innate immune system, which are also found in higher animals. What we find out about these pathways in C. elegans could apply to innate immunity in humans, Garsin said.

The bacterium appears to use some of the same virulence factors to cause disease in the millimeter-long worm as it does in mammals. Strains that dont kill the worms in Garsins experiments will be tested in mice. Identification of genetic differences between the virulent and weaker strains could provide avenues for drug discovery.

In a paper in the journal Science last year, Garsin and colleagues showed that a genetic variation in the worm that had been associated with a longer lifespan also confers resistance to E. faecalis and other disease-causing bacteria.

Worms with the genetic mutation enjoyed a five-fold increase in survival over those lacking the variation when both types were infected with E. faecalis.

The heightened resistance to pathogens contributes to the greater longevity of the mutant worms. A similar genetic variation already has been shown to extend the lifespan of mice.

A connection between longevity and resistance to infection makes sense. As people get older, they generally are more susceptible to infection, Garsin said. This is one genetic pathway that you might someday be able to target and achieve pathogen resistance and a longer, healthier life.

The Ellison award is recognition of Garsins ability to look at longstanding problems in new ways, said microbiology and molecular genetics department chairman Sam Kaplan, PhD. Not only is the worm model simple in concept but it is strikingly simple in experimental approach. Dr. Garsin has recognized those features and is but one of a handful or researchers in a field that is likely to take off dramatically within the next few years.

Garsin, who also is on the faculty of the graduate school of biomedical sciences, joined the medical school faculty in December after her post-doctoral fellowship at Harvard Medical School. One tie to the medical school predates her arrival. Garsin noted she has collaborated with one of the leaders in the field of antibiotic-resistant bacteria, Barbara Murray, MD, chief of the schools division of infectious diseases.

Source: University of Texas Medical School at Houston