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'Evolutionary forecasting' for drug resistance
Date:9/21/2009

he upcoming study, Shamoo's team will sequence the genome of each organism both before and after the test. In addition, they'll take daily samples of the bacteria from the vessel and hold onto those for analyses. The stored samples are essentially a fossil record of the organism's adaptation to the drug. Using these, investigators can piece together the molecular path to resistance.

To determine the order the mutations occurred in, the team will use a technique created by Rice's Sarah Wu, a Will Rice College senior majoring in biochemistry and cell biology who began working in Shamoo's lab as a freshman. Using an instrument called a mass spectrometer, Wu found a way to translate the molecular changes from a particular mutation to the molecular weights of samples analyzed with the mass spectrometer.

Shamoo said the technique is important because it will allow his team to determine which mutations occurred first and to build those changes into a network-style representation that show's how an organism adapts to a specific drug.

Once the team has identified the particular mutations that convey drug resistance, they'll use X-ray crystallography to try and determine the exact molecular modifications that occur in the proteins those genes encode.

"We're interested in building those physical relationships that show how molecules confer drug resistance," Shamoo said. "The idea is that if you understand the mutation and what the mutation does to an enzyme or protein, then you can understand how that helps increase the fitness of a population of bacteria."

Shamoo said the team hopes to find a general set of rules or patterns that bacteria follow as they evolve to become drug-resistant.

For example, while the specific mutations that allow bacteria to become drug-resistant may differ from strain to strain, there may be patterns or rules that govern the order in which mutations occur and the regions of genome in which they oc
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Contact: Jade Boyd
jadeboyd@rice.edu
713-348-6778
Rice University
Source:Eurekalert  

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