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Posted 08.27.04

MU Researchers Working to Create More Effective Antibiotics

COLUMBIA, Mo. -- According to the Centers for Disease Control, antibiotic resistance, or the ability of bacteria to resist drugs, has been called one of the world's most pressing health problems. Many research projects are developing methods to combat antibiotic resistance. A pair of research teams at the University of Missouri-Columbia is studying a resistant bacterium that can be particularly harmful or deadly to people with weakened immune systems.

MU researchers Lesa Beamer, associate professor of biochemistry and Peter Tipton, professor of biochemistry, are targeting Pseudomonas aeruginosa, a common bacterium that can be found in soil, water or even on a restaurant's salad bar, and has become resistant to antibiotics. Healthy humans typically don't have a problem with P. aeruginosa, but it does affect patients suffering from cystic fibrosis, burn victims and patients undergoing chemotherapy treatment for cancer, among others.

"Some bacteria contain enzymes that create a coating around the bacteria to prevent antibiotics from getting in to do their jobs," Beamer said. "The idea behind this project was to see if we could manipulate that coating to allow the antibiotic access to the bacteria."

To accomplish this, the labs headed by Beamer and Tipton are working with a particular set of enzymes, or proteins, in the bacteria to design an inhibitor, or small molecules that block these enzymes.

In order to stop enzymes from creating the protective coating, it is necessary to understand them in detail, Beamer said. Tipton studies the mechanics of how the enzymes work. Beamer is looking at the three dimensional structure of the enzymes and specializes in a procedure known as x-ray crystallography. This technique serves as a powerful substitute for a microscope, but allows Beamer to see things that are too small for the most powerful microscope. It offers her a 3-D view of the enzyme, helping her determine what portions of the enzyme are important and how they are arranged. Enzymes have a very specific job in a cell, and they have specific structures to do that job, she said.

Beamer and Tipton's research is ongoing, but Beamer said breakthroughs in developing structural descriptions of the enzymes have helped the researchers understand how the enzymes work and how the three-dimensional structure contributes to their function, which she hopes will lead to more effective antibiotics.

"There are quite a few bacteria that you could kill very easily 50 years ago with antibiotics that you either can't kill today, or they are harder to kill," Beamer said. "We want to find a way to make current antibiotics work better."


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