Lab is Developing Rapid Test for Cultivated Pathogens

Researchers at Rice University have won federal support to develop a genomic test that can quickly determine whether a disease outbreak is caused by a natural pathogen or one that was grown in a lab by terrorists.

The three-year grant -- Rice's first from the Defense Threat Reduction Agency -- is designed to provide homeland security and public health officials with the tools they need to quickly determine how to respond to an outbreak.

"In a natural outbreak, there are classic rules of epidemiology that describe how particular types of diseases will spread," said principal investigator Yousif Shamoo, associate professor of biochemistry and cell biology and director of Rice's Institute for Biosciences and Bioengineering. "In a man-made outbreak, you may be faced with an actor who is continuously spreading the disease, or you might have a person who's engineered strains knowing public health strategy."

The project's goal is to find telltale signs that an organism has become accustomed to living in a biology lab. Shamoo said that's possible because of the way bacteria evolve -- they can progress through hundreds of generations in just a few weeks and rapidly adapt to new conditions giving telltale signs of their domestication in a lab.

"Living out in the wild is a pretty rough existence," Shamoo said. "By comparison, life in the laboratory is very posh. You live in very nice conditions on agar plates eating this very rich media. And it's the same diet every day. Our expectation is that organisms will lose certain genes that allow them to get nutrition from the soil or the gut or wherever they came from, simply because they won't need them anymore."

Shamoo's lab specializes in studying how the process of evolution plays out at the molecular level. His group also studies how bacteria evolve to become drug resistant. He said the same forces that allow drug-resistant strains of a organism to outcompete their nondrug resistant cousins in a hospital will also allow his team to discern between pathogens whose origins are in nature or the lab.

"There's a cost to the organism to maintain its genes," Shamoo said. "If genes are no longer necessary, that presents an advantage for new strains that put more energy into dividing and growing, rather than maintaining unnecessary functions. Those strains will outcompete the wild-type, which will disappear from the lab within just a few generations."

For the DTRA project, Shamoo and his students will gather wild strains of two common bacteria -- Enterococcus faecalis and Escherichia coli -- and domesticate each of them in the lab. Genomic snapshots will be taken throughout the process, and they'll be analyzed for telltale patterns.

"You don't want to get into the business of trying to catalog the specific changes that take place for thousands of different organisms," Shamoo said. "The idea is to look for commonalities. Is there a common set of responses to domestication that you would likely see for any organism that's adapting from living in the wild to living in the laboratory?"

While E. faecalis and E. coli are each common, well-studied bacteria, they also come from opposite ends of their species' genetic spectrum. Due to fundamental differences in the chemical and physical properties of their cell walls, for example, they fall into very different classifications: E. faecalis is Gram-positive, and E. coli is Gram-negative.

The upshot is that if genetic patterns associated with domestication can be found in each of these, those same patterns are likely to be found in other bacteria, Shamoo said.

"There's nothing to stop us from going further with this," Shamoo said. "If we find something after three years, and we want to expand the pool to include soil bacteria, or other types, we can do that and see if the patterns repeat."

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