A new type of antibacterial agent that attacks its target at the genetic level may offer a fundamentally different way to battle bacteria that have developed resistance to antibiotics, researchers at Oregon State University say.

“It’s literally like throwing a wrench into the genes” of bacteria, said Bruce Geller, a professor of microbiology at OSU and lead author of a recently published study on the new agent, called a PPMO.

Researchers from OSU joined with colleagues from the University of Texas Southwestern Medical Center and Sarepta Therapeutics, a biotechnology company, on the study. (Sarepta used to be known as AVI Biopharma until a name change last year.)

The implications potentially are huge, especially in settings where bacteria have developed resistance to antibiotics, which usually function by disrupting the cellular operations of bacteria.

The study showed how PPMOs – the acronym is short for peptide-conjugated phosphorodiamidate morpholino oligomers – can work to directly silence the expression of specific genes in bacteria. The result: The bacteria stop growing and eventually die, Geller said.

“We think it just jams the machinery,” Geller said in a recent interview.

The PPMOs are synthesized to target specific genes, he said.

PPMOs have yet to be tested in humans – Geller said he thought those tests might still be five years or so away. But the study reported that in laboratory tests, the PPMOs were effective in battling A.baumannii, a dangerous strain of Acinetobacter, and one that’s especially resistant to antibiotics. That particular strain has infected hundreds of U.S. soldiers since the start of the Iraq War.

Bacteria have been around for some 3.5 billion years – “they’ve got a head start on us,” Geller said – and have been remarkably adept at developing resistance to antibiotics. We haven’t helped matters by being overly reliant on traditional antibiotics.

That reliance on antibiotics has come with another price: They don’t always discriminate between harmful and beneficial bacteria, and we’re just starting to get a better handle on the link between good health and beneficial bacteria. “Most people don’t know that bacteria are required for good health,” Geller said.

The PPMOs, however, can be crafted to target specific genes on specific bacteria – leaving beneficial organisms untouched.

And the basic technology can be used, in theory, to treat other diseases with an underlying genetic component.

Geller said he’s hoping to line up additional funding from the National Institutes of Health for follow-up studies to develop PPMOs to battle the bacteria that cause chronic middle-ear infections in children and also to fight the bacterial infections that frequently afflict victims of COPD, the third-leading cause of death in the United States.

The PPMOs “open up a whole new world of targets” for treatment, Geller said. “If you give us bacteria, and tell us what the gene sequence is, we can attack it.”

David Stauth of Oregon State University News and Research Communications contributed information for this story.

Mike McInally is the editor of the Democrat-Herald. He can be reached at 541-812-6097 or mike.mcinally@lee.net

(1) comment

Jon Moulton
Jon Moulton

The PPMOs are based on Morpholino oligos. http://en.wikipedia.org/wiki/Morpholino

This new paper builds on a body of work inhibiting bacterial growth with Morpholino oligos (PMO) and their peptide conjugates (PPMO), mostly from Bruce Geller's lab: http://www.gene-tools.com/node/45

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