Scientists develop molecules that could stop bacteria in their tracks
April 5, 2006
By Christina Dierkes
Bacteria have grown tough. Hospitals frequently battle patient infections, and bacteria resistant to conventional antibiotics don't make the job any easier. That's prompted scientists to seek new ways to eliminate these dangerous bugs.
Researchers at Ohio University and Ohio State University have discovered that a target sequence of RNA can be disrupted by small synthetic molecules. This disruption could effectively shut off the bacteria and kill them. RNA, which is closely related to DNA, relays genetic information from one area of the cell to another.
The target sequence controls the production of proteins necessary for the bacteria's survival through the interaction of two forms of RNA, says Jennifer Hines, an Ohio University associate professor of biochemistry involved with the project. Interrupting that production could kill bacteria such as staphylococcus, the largest source of infection in hospitals, as well as anthrax and the bacterium that causes tuberculosis, she says.
Ohio State University scientists Tina Henkin and Frank Grudy, Stephen Bergmeier, associate professor of chemistry at Ohio University, and Hines have identified a small number of molecules that can bind to this RNA "switch" in the bacterial genetic sequence. The research team initially created a library of different types of molecules with a variety of chemical structures, and tested each molecule to see which one would best stick to the target RNA sequence. They've reported on this model system in the Journal of Molecular Biology.
The team's focus now has turned to creating a specific molecule that can recognize the RNA features of the sequence, called the T box transcription antitermination system, which eventually could become the basis of a drug that could be used in further testing.
The targeted molecule would disrupt the normal process of transcription and translation, which is the process of transcribing the genetic code contained in the bacteria and then using that information to form proteins.
"The proteins expressed by this process are then involved in the production of necessary materials for the cell. Anything that disrupts this flow of information or the balance of expression can be potentially harmful to the cell," says Hines, whose team's research is funded in part by the National Institutes of Health, the Battelle Memorial Institute's SOSCI Project, and Ohio University. The researchers have filed for a patent for some of the compounds they developed.
The advantage of this type of treatment, compared to conventional antibiotics, is that one group of related molecules potentially could be created to target several bugs, as the T box antitermination system has similar attributes in various forms of bacteria. Use of this potential treatment - which is still several years away from clinical use - also could reduce the incidence of bacterial resistance. With other antibacterial agents, "all that is needed to develop resistance is to mutate a single point [in the bacteria's genetic code] to prohibit the drug from binding," Hines says. To thwart the new treatment, "multiple genes in the bacteria would have to be simultaneously mutated, the likelihood of which is extremely small," she says.
Another advantage of creating this type of treatment option is that the molecule would target only this cellular system, which is not present in human cells, and would reduce potential toxic side effects. This would benefit patients who have developed allergies to antibiotics, the symptoms of which can be just as dangerous as the disease that needed to be treated in the first place.
Christina Dierkes is the graduate assistant in the Office of Research Communications. This story will appear in the forthcoming Spring/Summer 2006 issue of Perspectives magazine.