Genetically Modified Bacteriophages: A New Tactic Against Antibiotic Resistance

With 2 million cases of antibiotic-resistant infections occurring each year in the United States, the threat of antimicrobial resistance (AMR) is very real. The pipeline for drug development is perilous and running dry, and there are increasing challenges for combatting resistance with stewardship initiatives. How do you change prescribing and usage practices across several industries? In the face of these overwhelming odds, many are pointing to a new form of treatment for resistant infections—bacteriophages.

Using bacteriophages, which are bacterial viruses that invade the bacterial cells and cause the bacterium to lyse or break down, against AMR isn’t an entirely new concept, but is growing in popularity. As we face a new era in infection prevention and disease control, many are pointing to forms of treatment, like bacteriophages, to treat the increasing prevalence of resistant organisms. One recent case, though, is drawing considerable attention to the use of bacteriophages, namely because the phages were genetically engineered.

Investigators recently published the success of their use of engineered bacteriophages against a disseminated, drug-resistant Mycobacterium abscessus in a teenage patient. In their article in Nature Medicine, the investigators discusses how the 15-year-old patient battled a disseminated infection that left her near death. The study team took a chance that this novel approach would work. Thankfully, it did.

The patient was given the experimental treatment after acquiring a resistant infection with Mycobacterium abscessus following a lung transplant. It is common for patients with cystic fibrosis to acquire drug-resistant lung infections and, in many cases, these can lead to death.

The investigators tried a 3-phage intravenous cocktail that was developed by genome engineering and forward genetics. Graham Hatfull, PhD, a professor in the department of Biological Sciences at the University of Pittsburgh, was 1 of the investigators working to help identify a phage for usage, employing his students to go through 15,000 phages to help identify 1 that would give the patient a fighting chance.

“He identified 1 that appeared to be good at killing the bacterium, Mycobacterium abscessus, which was causing the girl's infection (as it turns out, the phage he identified, known as ‘Muddy,’ was discovered in a rotting eggplant),” NPR reported. “Hatfull's team also identified 2 other phages that could be useful, which they then genetically modified in a way they hoped would boost their ability to zero in on and kill the bacterium attacking the teen.”

Following genome editing, they created the 3 treatment cocktails for use and began infusing 1 billion phages into the patient twice a day. From intravenous infusion to putting the cocktail directly onto her skin lesions, they went all in on this novel approach. Waiting with bated breath, they saw the infection start to retreat. Although it’s not entirely gone and the patient is still receiving daily phage infusions, it has been remarkably successful in battling the infection. As doctors continue the treatments, the hope is that the infection will eventually and fully dissipate and that “Muddy” will prove a formidable enemy against other resistant infections.

The application of a genetically modified bacteriophage to battle multidrug-resistant infections is something that could not only change the survival rate of cystic fibrosis patients, but also the world in its efforts against AMR. These findings should encourage us to put more focus into these novel approaches. Ultimately, it behooves us to think outside the box when it comes to the sinister Frankenstein we’ve created.