As the world experiences a wakeup call about the rise of drug-resistant infections, a new approach to creating smarter, “programmable” drugs could combat the two major problems with life-saving drugs today.
On the one hand, today’s antibiotics work a little too well. They not only kill infections, they wipe out the body’s entire microbial ecosystem, the good bacteria with the bad. As scientists learn more about how the composition of every person’s unique microbiome affects his or her health, from our immune systems to our propensity towards obesity, they are realizing that the way antibiotics kill everything in its path could hurt long-term health.
On the other hand, today’s antibiotics aren’t working well at all. The number of antibiotic-resistant infections is on the rise and some are almost entirely untreatable with existing drugs. According to the CDC, antibiotic-resistant infections caused 23,000 deaths and 2 million illnesses in the U.S. each year. The White House’s release in September of a national strategy to address these growing concerns calls them not only a top public health priority but a national security one as well.
“Bacterial infections are becoming more difficult. They are becoming antibiotic resistant, and also the indiscriminate use of antibiotics has side effects that are much more clear now than they were before,” says Luciano Marraffini, a bacteriologist at New York’s The Rockfeller University.
Marraffini is leading research that takes a new approach. He aims to target only the disease-causing bugs in our bodies, specifically the ones that are resistant to more traditional antibiotics. In a recent experiment described in a study in Nature Biotechnology, he and his team used their smarter drugs to selectively rid mice of an antibiotic-resistant Staph infection on their skin.
Typical antibiotics work by damaging or interfering with a bacteria’s cell wall or membrane, killing the organism or disrupting its ability to reproduce while leaving human cells intact. But they aren’t very specific to any particular species or strain.
Marraffini’s antibiotics are specific: They use an enzyme, inserted inside a virus, that is coded to attack only germs with a specific sequence of DNA. That coding can be changed relatively easily to match the infection a doctor is trying to target. The virus delivers the enzyme inside all kinds of bacterial cells, but then the enzyme will only cleave the bacteria’s chromosome if it’s a DNA match. That way it won’t kill all bacteria inside the body–only the one its targeting. It would be relatively difficult for germs to evolve a permanent resistance to this kind of antibiotic, Marraffini says.
With Timothy Lu, an MIT researcher working on a similar idea, Marraffini plans to launch a company to try to commercialize the work. However, there would be a long road ahead. The major challenge is that viruses used in the study are not a very practical method to deliver the killer enzyme into the bacterial cells–the viruses themselves can illicit an immune response from the human body and it would be hard to figure out a precise dosage, among other concerns.
“In order to make it really useful, we will have to figure out a delivery system that is different,” Marraffini says. “This is a proof of principle that this can work.”