March 16, 2009

Antibiotics that don’t trigger resistance

U.S. researchers say they are developing a new generation of antibiotic compounds that do not provoke bacterial resistance.

Researchers at Albert Einstein College of Medicine of Yeshiva University say the compounds work against two notorious microbes -- Vibrio cholerae, which causes cholera, and E. coli 0157:H7, the food contaminant that causes approximately 110,000 illnesses and 50 deaths a year in the United States.

Senior author Vern Schramm says antibiotics initially work extremely well, killing more than 99.9 percent of microbes they target. But through mutation and the selection pressure exerted by the antibiotic, a few bacterial cells inevitably manage to survive, repopulate the bacterial community and flourish as antibiotic-resistant strains.

Rather than killing Vibrio cholerae and E. coli 0157:H7, the researchers aimed to disrupt their ability to communicate through quorum sensing. Many species of bacteria use quorum sensing to coordinate their gene expression according to the local density of their population.

The researchers targeted a bacterial enzyme, MTAN, which is directly involved in synthesizing the autoinducers crucial to quorum sensing. The researchers designed a substrate to which MTAN would bind much more tightly than to its natural substrate -- so tightly, in fact, that the substrate analog permanently locks up MTAN and inhibits it from fueling quorum sensing.

The findings are published in the journal Nature Chemical Biology.