Scientists discover potential new way to control drug-resistant bacteria

September 22, 2004

Based on an improved understanding of bacteriophages--viruses that infect bacteria--scientists reporting in the Sept. 23 issue of the journal Nature believe they have discovered a potential new way to control drug-resistant bacteria, an increasingly worrisome public health problem.

The new research, funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, found that bacteriophages contain genes that allow them to quickly change their proteins to bind to different cell receptors. The researchers, who encountered this genetic property while working on an unrelated project, believe that this discovery could lead to the use of genetically engineered phages to treat bacterial infections that have become resistant to antibiotics.

"This serendipitous finding underscores the importance of basic research," says Anthony S. Fauci, M.D., director of NIAID. "With our increased understanding of how bacteriophages work, we can potentially tailor these viruses to infect and destroy bacteria that have mutated and become drug-resistant."

"This powerful and innovative research opens up numerous possibilities for developing drugs and vaccines that can control resistant bacteria, which are a growing public health concern," says David L. Klein, Ph.D., who oversees bacterial respiratory disease research at NIAID. "The introduction of bacteriophages may also lead to a unique approach against biodefense-related pathogens."

The discovery was made by researchers at the University of California Los Angeles led by Jeffrey F. Miller, Ph.D., professor and chair of microbiology, immunology and molecular genetics. Dr. Miller's team found that the genome of the phage that infects Bordetella bronchiseptica, a relative of the bacterium that causes whooping cough, contains a series of genes that change the part of the virus that binds to the bacterial cell. These genes allow the phage to rapidly evolve new variants that can recognize and attack bacteria that may have become resistant to the previous phage.

"Phage therapy has been practiced for nearly a hundred years in parts of the world, and even in the United States in the first half of the 20th century," says Dr. Miller. "But now we think we can engineer bacteriophages to function as 'dynamic' anti-microbial agents. This could provide us with a renewable resource of smart antibiotics for treating bacterial diseases."

Dr. Miller says that he and his team are continuing to study this genetic mechanism to learn more about its biochemical properties and to determine whether higher forms of life have similar classes of genes. He believes that, in time, they will be able to use the knowledge gleaned from this discovery to generate proteins in the laboratory that will bind to almost any molecule of interest.
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NIAID is a component of the National Institutes of Health, an agency of the U.S. Department of Health and Human Services. NIAID supports basic and applied research to prevent, diagnose and treat infectious diseases such as HIV/AIDS and other sexually transmitted infections, influenza, tuberculosis, malaria and illness from potential agents of bioterrorism. NIAID also supports research on transplantation and immune-related illnesses, including autoimmune disorders, asthma and allergies.

Reference: J F Miller et al. Tropism switching in Bordetella bacteriophage defines a family of diversity-generating retroelements. Nature 431: 476-81 (2004).

Press releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.

NIH/National Institute of Allergy and Infectious Diseases

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