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Bacteria key to cures?

U. scientists look to sea to develop medicines

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The bacteria that live with and help small sea creatures like sea squirts and sponges may be key to producing drugs that fight cancer and other diseases, according to researchers led by a University of Utah medicinal chemist.

They hope to figure out the genetic process by which the bacteria produce different compounds, some of which have been isolated and shown to have potent activity against cancer cells, said Eric W. Schmidt, assistant professor of medicinal chemistry in the U. College of Pharmacy and senior author of the study published Nov. 5 in Nature Chemical Biology online.

The research focused on small sea creatures in the tropical Pacific Ocean that have bacterial symbionts living with them. They took bacteria samples from three locations, including one near the Philippines, one in Papua, New Guinea, and one in the Solomon Islands. They looked particularly at sea squirts, an invertebrate that lives on rocks and coral. The little creatures live with the symbiotic bacteria, which are thought to provide nutrients to the sea squirts through photosynthesis. The bacteria also produce compounds that, besides showing anti-cancer properties, may also help protect the sea squirts from predators.

The search for medicine from sea life isn't new. As many as 20 potential drugs created by marine organisms are now in clinical trials, Schmidt said. But it's extremely difficult to produce adequate supplies by going to the bioreef to collect it from sea animals. It's simply impractical. The researchers believe they can use the bacteria in the lab for larger-scale production.

They have already figured a way to use genetic pathways in the bacteria to produce compounds.

"We're interested not in how to produce individual compounds, which is laborious, but in how these pathways evolve," Schmidt said. "There is huge diversity of compounds that are related to each other and we are interested in how an organism that makes one compound will, with a slight genetic change, make a different one. If we can understand how that change takes place, we can make new compounds using that evolutionary model."

Most drugs start out as natural compounds, he said, then a chemist figures out how to make it in the lab. In this case, the researchers want to use genetic engineering to get the bacteria to produce the compound for them.

"We're hoping we can find a way to make natural molecules of compounds through single mutations in DNA," Schmidt said. They have already found some mutations that change what kind of compound is made. Aping that process, they made an entirely different compound.

They are developing techniques to make very large numbers of compounds and plan to use them in ongoing cancer and HIV research to see if they're possible treatments for human disease.

They also want to see if what they've learned about the bacteria holds up universally or if there are different rules for different compounds.

Collaborators on the study include Margo G. Haywood, from the Oregon Health Sciences University; Sebastian Sudek, from the Scripps Institution of Oceanography at the University of California, San Diego; M.J. Rosovitz and Jacques Ravel, both of the The Institute for Genomic Research, Rockville, Md.; and Mohamed S. Donia and Brian J. Hathaway, both of the Department of Medicinal Chemistry, U. College of Pharmacy.

E-mail: lois@desnews.com