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UT Southwestern researchers say new approach to treating drug-resistant infections looks promising

Monday December 9, 2013
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A new type of antibiotic called a PPMO, which works by blocking genes essential for bacterial reproduction, successfully killed a multidrug-resistant germ common to healthcare settings, UT Southwestern Medical Center researchers report.
The technology and new approach offer potential promise against the growing problem of antibiotic resistance, researchers said.

Acinetobacter infection mainly affects hospitalized patients or those in long-term care facilities, such as those on ventilators or with urinary catheters or patients treated for open wounds. In the study in the Oct. 15 issue of the Journal of Infectious Diseases, PPMOs designed to combat two strains of Acinetobacter reduced the number of infectious bacteria in mice by more than 90%. Survival of infected mice also improved with the treatment. One of the targeted strains was A. baumannii, which accounts for about 80% of reported Acinetobacter infections, according to the news release.

“We set out to target specific genes in Acinetobacter in an effort to inhibit the bacterium’s growth,” said David Greenberg, MD, assistant professor of internal medicine and microbiology and senior author of the study, said in a news release. “With infections from drug-resistant pathogens rising rapidly, there is an urgent need to come up with new approaches such as the use of PPMOs to spur antibiotic development.”

The technology that created the synthetic PPMO could be used to develop similar antibiotics targeting other bacteria and viruses, he added. “We believe there is a lot of promise in developing new antibiotics that target specific pathogens as opposed to so-called broad-spectrum antibiotics that target whole classes of bacteria,” Greenberg said.

Whereas broad-spectrum antibiotics can kill off multiple pathogens, PPMOs are pathogen-specific and work by silencing essential genes that help that particular strain of bacteria or virus grow. A PPMO, or peptide-conjugated phosphorodiamidate morpholino oligomer, mimics the structure of a nucleic acid and binds to mRNA, preventing the formation of proteins. PPMOs have not been tested in humans, although a compound of similar chemical structure is being tested as a therapy in Duchenne muscular dystrophy patients.

More research is needed before the PPMOs are ready for human testing, said Greenberg, who was assisted in the study by Kimberly Marshall-Batty, a senior research associate in internal medicine. Future studies will involve development and testing of PPMOs targeting other specific bacteria and virus types. Researchers also may try to create a PPMO that silences genes involved in antibiotic resistance.

The study involved researchers from UT Southwestern, Oregon State University and Sarepta Therapeutics, Inc., a Massachusetts-based pharmaceutical company that supplied the PPMOs for testing. Support for the study was provided by the National Institutes of Health.


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