119-AP-99
EMBARGOED UNTIL 11 A.M. PDT, THURSDAY, OCT. 14, 1999
NEWLY DISCOVERED ANTIBIOTIC PROTEIN IN ANIMALS COULD RESULT IN NEW WEAPONS FOR FIGHTING INFECTIONS
Protein Made by Two Separate Genes Challenges Assumptions About How Proteins are Made
Irvine, Calif. -- A UC Irvine College of Medicine research team has found a powerful antibiotic protein in animals that could be used to design new types of drugs to fight infections. The researchers also found that the protein is produced ultimately from two distinct genes, a discovery that challenges traditional assumptions about how proteins are made.
The small, circular protein, called RTD-1, is an effective killer of bacteria and fungi and has never been seen in animals before. It most closely resembles circular proteins that work against viruses and have been seen only in tropical plants. The discovery of this protein in animals could potentially result in new treatments against infections in humans. The findings appear in the Oct. 15 issue of Science.
Dr. Michael Selsted, professor of pathology, and his colleagues at UCI and UC Davis found RTD-1 in the white blood cells of rhesus monkeys. The researchers also found that half of the RTD-1 protein was produced by one gene and the other half by a completely different gene in the white blood cells. The two parts of the protein were then combined by chemically fusing the head of one half to the tail of the other half in the cell to produce RTD-1.
RTD-1 is a member of a class of proteins called defensins, which are naturally occurring anti-infection agents found in both animals and plants. Until this discovery, defensins were never known to have circular structures; RTD-1 is found to be most effective at fighting infections in its circular form.
"The discovery of this protein in animals shows us a new type of molecular weapon used by the body to fight infection," Selsted said. "Since it appears to work similarly to other antibiotic defensins in animals and plants, we may be able to use it to design new types of antibiotics."
RTD-1 was found in white blood cells that specialize in engulfing and destroying bacteria and other microscopic invaders. White blood cells use many tools to kill these microbes; the UCI research adds RTD-1 to the cells' arsenal of defensins, which work by disrupting invading cells' membranes. Selsted's team found RTD-1 to be an unusually powerful antibiotic and anti-fungal agent. Minute amounts were able to destroy infectious bacteria like staphylococcus and E. coli and fungi that cause opportunistic infections associated with AIDS.
One unique feature Selsted's team found was that RTD-1, unlike many other natural infection fighters, is not weakened by salt. The researchers suggest that this feature could prove useful against certain infections in which high salt levels inhibit other types of defensins. For example, some researchers believe that the defensins are inactivated in the lungs of cystic fibrosis patients because of high salt concentrations in their bodies.
The protein also is the first example found of a single protein that is made by two distinct genes. Typically, one single strip of DNA makes up a genetic code that ultimately creates one protein.
"The discovery that the products of two genes are spliced together demonstrates that we still have much to learn about how proteins are made," Selsted said. "RTD-1 is also the first of its kind of be found in animals and its genes are related to genes that make other defensins. We think, therefore, that the body's ability to make these circular antibiotic proteins is not limited to RTD-1."
Selsted's team is now looking at how cells create the circular RTD-1, how its production can be stimulated in the laboratory and how RTD-1 could be used to create anti-infection drugs.
"Cystic fibrosis is just one of many diseases that could be combated by a drug derived from RTD-1," Selsted said. "Not only could future research on RTD-1 result in new antibiotics, but the way these circular proteins are produced may offer us novel ways to create proteins that could be useful as drugs."
Selsted was assisted in his research by Professor Andre Ouellette and researchers Yi-Quan Tang, Jun Yuan, George Osapay, Klara Osapay and Dat Tran at UCI, and by Christopher J. Miller, professor of veterinary medicine at UC Davis. The research was supported by funding from the National Institute of Allergy and Infectious Disease and from Biosource Technologies, Inc., a pharmaceutical firm in Vacaville, Calif.
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Contact: Andrew Porterfield
(949) 824-3969
[email protected]
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