"Molecular wedge" renders superbugs vulnerable to antibiotics again
We’re locked in an arms race with bacteria – and worryingly, it looks like we’re losing, as they increasingly develop resistance to our best drugs. Now, scientists at the University of Oklahoma have identified a new class of molecules that disable a major superbug weapon, which could make existing antibiotics effective again.
For much of human history, bacterial infections were a common part of life, and often deadly. But in the early 20th century, scientists discovered a new class of bacteria-fighting medicine, starting with penicillin. These antibiotics helped scientists and doctors perform procedures much more safely and effectively than ever before, and reduce the deadliness of infections like tuberculosis.
But of course, things didn’t stay so rosy. Bacteria are proficient adapters, rapidly evolving defenses against each drug we threw at them, so we had to keep developing new ones. Over time, we’ve exhausted our arsenal to the point where there are now “superbug” bacteria that are completely resistant to every antibiotic we have, and the production line of new ones is drying up. This threatens us with a future where once-routine infections become potentially deadly again.
Now, scientists have demonstrated a new way to counter one of the most effective bacterial defense strategies. Some species have evolved efflux pumps – proteins on the bacterial membrane that flush out antibiotic molecules that try to enter the cell. This has worked well for the superbugs so far, but the team has now identified molecules that effectively inhibit these efflux pumps.
The scientists discovered that these inhibitors work like a “molecular wedge,” driving themselves between the inner and outer cell membranes of the bacteria. That prevents the protein parts of the pump from sending signals to each other in response to the presence of a drug, which lets the antibiotic go to work in the cell. The team says these molecules could be administered alongside existing antibiotics to make the drugs effective once again.
“We already live in a post-antibiotic era, and things will get much worse unless new solutions are found for antibiotic resistance in clinics,” said Helen Zgurskaya, lead author of the study. “The discoveries we’ve made will facilitate the development of new treatments to help mitigate an impending crisis.”
The research was published in the journal Nature Communications.
Source: University of Oklahoma