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Genetic-Based Antibiotic Found Effective in Lab Tests

Acinetobacter baumanii

Acinetobacter baumanii, one of the strains tested with PPMOs by the research team ( F. Silveira, NIH)

Researchers at Oregon State University, University of Texas Southwestern Medical Center, and the biotechnology company Sarepta Therapeutics tested in lab mice an antibiotic developed from synthetic genetic material that kills bacteria resistant to traditional antibiotics. Their findings appear online today in the Journal of Infectious Diseases (paid subscription required).

The team from the labs of microbiologists Bruce Geller at Oregon State in Corvallis and David Greenberg at Southwestern in Dallas, with colleagues from Sarepta, also in Corvallis, tested a new type of anti-bacterial agent known as peptide-conjugated phosphorodiamidate morpholino oligomers or PPMOs. These agents are synthesized analogues of DNA and RNA designed to stop the functioning of specific genes, in this case essential genes in two strains of the Acinetobacter bacteria.

Acinetobacter is a notorious bacteria, associated with infections in health care facilities, especially those that treat very ill patients, such as intensive care units. It has also been found in many military medical care units treating service members in Iraq and Afghanistan. Besides striking highly vulnerable populations, Acinetobacter is also now resistant to many conventional antibiotics.

PPMOs, say the researchers, offer a different technique for attacking bacteria. Conventional antibiotics work by disrupting the cellular functions of bacteria, which can affect other micro-organisms subjected to the treatment, sometimes with unwanted effects. PPMOs, on the other hand, address specific genetic functions unique to the bacteria, and thus offer more precise targeting of the therapy.

The Oregon State/Southwestern team tested PPMOs supplied by Sarepta that target specific messenger RNA generating vital proteins in acinetobacter bacteria in mice infected with two strains of acinetobacter. The results show the PPMOs reduced the number of infections in test mice by 90 percent, and reduced inflammation and increased survival of the mice, compared to control substances.

While PPMOs have not yet been tested in humans, the underlying phosphorodiamidate morpholino oligomer (PMO) chemicals have been tested and found safe, according to a statement from Oregon State. The addition of peptides that turn PMOs into PPMOs will need to be tested further for safety in animal models and clinical trials.

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