Potential new targets for antibiotics

Nov 1 2005

A new study of genetic changes in bacteria may ultimately help drug makers stay a step ahead of disease-causing bacteria that can become resistant to antibiotics.

The secret lies in understanding the function of the ribosome, a tiny protein-making factory residing inside most cells.

Many currently used antibiotics alter a ribosome's ability to make proteins, said Kurt Fredrick, a study co-author and an assistant professor of microbiology at Ohio State University.

But he and his colleagues at the University of Illinois thought that there may be additional places in a ribosome that future antibiotics could affect, places that current antibiotics don't currently target.

The researchers were right.

"Antibiotic resistance will always be an issue," Fredrick said. "But as long as we can stay ahead of the ability of the pathogens to resist antibiotics, we're okay."

The findings appear online this week in the Early Edition of the Proceedings of the National Academy of Sciences. Fredrick co-authored the study with lead author Alexander Mankin and with Aymen Yassin, both with the University of Illinois at Chicago.

Fredrick provided a strain of Escherichia coli important for the study.

In order to find out if their initial hunch was correct - that there actually are other "hot spots" on a ribosome that could act as potential targets for antibiotics - the researchers first introduced a mutated copy of the ribosomal genes into E. coli cells and looked for those rare mutations that could interfere with cell growth. It was known from previous studies that such deleterious mutations occurred within critical regions of the ribosome.

After identifying dozens of deleterious mutations, the researchers were able to produce a composite map showing where these mutations were positioned on the ribosomes. Interestingly, the map indicated that there were four additional places on ribosomes where these mutations clustered. While researchers already knew that these sites existed, they did not know that these areas could possibly become targets for antibiotics.

These sites are what may one day give pharmaceutical companies an edge in creating new antibiotics in order to keep ahead of bacteria's clever way of developing resistance to antibiotics.

"Now that we know these other sites exist and that they could be potential targets for antibiotics, the next step is to figure out how exactly these mutations interfere with the cell's own ribosomes," Fredrick said.