“We’ve lost the ability to use many of our mainstream antibiotics,” said Bruce Geller of Oregon State University. “Everything’s resistant to them now."
Making modifications to existing antibiotics runs the risk that bacteria will simply mutate and become resistant to the new, chemically modified antibiotic.
That progression has made carbapenems, the most advanced penicillin-type antibiotic, the last line of defense against bacterial infection.
By contrast, the discovered molecule does not directly fight the bacteria. Instead, it inhibits the production of an enzyme that makes bacteria resistant to a wide range of penicillins.
The molecule is a peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO). It combats the enzyme called New Delhi metallo-beta-lactamase (NDM-1). This enzyme is accompanied by genes that encode resistance to most antibiotics.
"We’re targeting a resistance mechanism that’s shared by a whole bunch of pathogens,” explained Geller.
"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 colistin is the last antibiotic that can be used on an NDM-1-expressing organism, but that bacteria are now completely resistant to it.
“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," Geller said.
In vitro, the new PPMO restored the ability of meropenem (an ultra-broad-spectrum drug of the carbapenem class) to fight three different genera of bacteria that express NDM-1.
Geller has been researching molecular medicine for more than a decade. He said the study's findings will likely be ready for testing on humans in about three years.
