Researchers with Oregon State University (OSU) have identified a molecule that neutralizes germs' resistance to antibiotic.
Known as a PPMO, short for peptide-conjugated phosphorodiamidate morpholino oligomer, the molecule has shown ability to inhibit expression of an enzyme, known as NDM-1, short for New Delhi metallo-beta-lactamase, that makes bacteria resistant to a wide range of penicillins.
The study demonstrated that in vitro the new PPMO restored the ability of an ultra-broad-spectrum drug of the carbapenem class, called meropenem, to fight three different genera of bacteria that express NDM-1, and 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.
"We're targeting a resistance mechanism that's shared by a whole bunch of pathogens," Bruce Geller, professor of microbiology in OSU's College of Science and College of Agricultural Sciences, was quoted as saying in a news release. "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."
While the results were published in the Journal of Antimicrobial Chemotherapy, Geller said 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 explained. "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. So 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 made the carbapenems, the most advanced penicillin-type antibiotic, the last line of defense against bacterial infection.
"The significance of NDM-1 is that it 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."
Geller added: "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."
