PPMO Has the Ability to Stop Resistance to Antibiotics
Scientists at OSU were part of an international collaboration that demonstrated the molecule’s ability to inhibit expression of an enzyme that makes bacteria resistant to a wide range of penicillins. The molecule is a PPMO, short for peptide-conjugated phosphorodiamidate morpholino oligomer. The enzyme it combats is known as New Delhi metallo-beta-lactamase, or NDM-1, and it’s accompanied by additional genes that encode resistance to most if not all antibiotics.
“We’re targeting a resistance mechanism that’s shared by a whole bunch of pathogens,” said Bruce Geller, professor of microbiology in OSU’s College of Science and College of Agricultural Sciences, who’s been researching molecular medicine for more than a decade. “It’s the same gene in different types of bacteria, so you only have to have one PPMO that’s effective for all of them, which is different than other PPMOs that are genus specific.”
The Oregon State study showed that in vitro the new PPMO restored the ability of an antibiotic -- in this case meropenem, an ultra-broad-spectrum drug of the carbapenem class -- to fight three different genera of bacteria that express NDM-1. The research also demonstrated that a combination of the PPMO and meropenem was effective in treating mice infected with a pathogenic strain of E. coli that is NDM-1 positive. Geller says the PPMO will likely be ready for testing in humans in about three years.
“We’ve lost the ability to use many of our mainstream antibiotics,” Geller said. “Everything’s resistant to them now. That’s left us to try to develop new drugs to stay one step ahead of the bacteria, but the more we look the more we don’t find anything new. That’s left us with making modifications to existing antibiotics, but as soon as you make a chemical change, the bugs mutate and now they’re resistant to the new, chemically modified antibiotic.” That progression, Geller explains, made the carbapenems, the most advanced penicillin-type antibiotic, the last line of defence against bacterial infection.
“The significance of NDM-1 is that it is destroys carbapenems, so doctors have had to pull out an antibiotic, colistin, that hadn’t been used in decades because it’s toxic to the kidneys,” Geller said. “That is literally the last antibiotic that can be used on an NDM-1-expressing organism, and we now have bacteria that are completely resistant to all known antibiotics. But a PPMO can restore susceptibility to antibiotics that have already been approved, so we can get a PPMO approved and then go back and use these antibiotics that had become useless.”
In addition to Geller, the research team included Oregon State postdoctoral scholars Erin Sully and Lixin Li and OSU undergraduate student Christina Moody, as well as scientists from Sarepta Therapeutics, Harvard Medical School, the University of Fribourg, and the University of Texas Southwestern.
This article has been republished from materials provided by Oregon State University. Note: material may have been edited for length and content. For further information, please contact the cited source.
Synthetic DNA Shuffling Enzyme Outpaces Natural CounterpartNews
A new synthetic enzyme, crafted from DNA rather than protein, flips lipid molecules within the cell membrane, triggering a signal pathway that could be harnessed to induce cell death in cancer cells. Researchers say their lipid-scrambling DNA enzyme is the first in its class to outperform naturally occurring enzymes – and does so by three orders of magnitudeREAD MORE
Simple Sugar Prevents Neurodegeneration in Lysosomal Storage DiseaseNews
New therapeutic approach may one day delay neurodegeneration typical of a disease called mucopolysaccharidoses IIIB (MPS IIIB)READ MORE
Eating Activates Calorie-Burning FatNews
The importance of the human brown adipose tissue (BAT) has become clearer during the past ten years. Coldness is one of the most effective activators of the BAT metabolic function but, in rodents, eating has also been shown to activate BAT. The debate on whether eating has the same effect on humans has lasted for decades. Now, the researchers at Turku PET Centre have proven that having a meal increases oxygen consumption in human BAT to the same extent as coldness.READ MORE