New molecule knocks out superbugs' immunity to antibiotics
"We've lost the ability to use many of our mainstream antibiotics," says Bruce Geller, one of the study's authors. "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."
Some of the most devastating bacteria get their antibiotic resistance by producing an enzyme known as New Delhi Metallo-beta-lactamase (NDM-1). It's this enzyme that the new research is targeting, by developing a molecule called a peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO). This inhibits the bacteria's expression of NDM-1, essentially destroying its antibiotic resistance and allowing existing drugs to be effective once again.
"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 explains. "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."
The study combined the new PPMO with meropenem, a type of carbapenem antibiotic that's effective against a broad range of bugs, and pitted it against three different types of bacteria that make use of NDM-1. In all cases, the PPMO restored meropenem's ability to kill the bacteria in vitro, and also managed to kill off an NDM-1-expressing strain of E. coli in tests in mice.
"We're targeting a resistance mechanism that's shared by a whole bunch of pathogens," says Geller. "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."
Geller says the new drug should be ready for human testing in about three years. The research was published in the Journal of Antimicrobial Chemotherapy.
Source: Oregon State University
ΑΝΑΔΗΜΟΣΙΕΥΣΗ ΑΠΟ ΤΟ FUTURESCOPE.COM 29/1/2017
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου