For nearly a century, antibiotics have transformed modern medicine. They make routine surgeries safer, protect cancer patients with weakened immune systems, and save countless lives from bacterial infections each year.

But that foundation is beginning to crack.

“Antibiotics are a cornerstone of modern medicine,” said Daria Van Tyne, PhD, associate professor of medicine in the Division of Infectious Diseases. “There are fundamental parts of medicine that don’t work if antibiotics don’t work.”

As antibiotic-resistant bacteria continue to spread, and fewer new antibiotics are being developed, physicians are increasingly confronted with infections that have become extraordinarily difficult, and sometimes impossible, to treat.

Now, with a new National Institute of Allergy and Infectious Diseases (NIAID) Program Project (P01) grant, Van Tyne is helping lead a national effort to develop an entirely different way to fight bacterial infections: bacteriophage, or phage, therapy.

The Pitt Center for Accelerating Phage Therapy (P-CAPT), co-directed by Van Tyne and Alexander Sulakvelidze, PhD, of Intralytix, Inc., is one of just three newly established Centers for Accelerating Phage Therapy to Combat ESKAPE Pathogens (CAPT-CEP) funded by NIAID. Together, the centers will develop the tools and scientific foundation needed to move phage therapy closer to routine clinical care.

Nature’s Predators

For people unfamiliar with phage therapy, Van Tyne starts with a simple explanation.

“I usually say that phages are the natural predators of bacteria,” she said.

Like the viruses that cause illnesses such as influenza or COVID-19, phages infect living cells. The difference is that they infect only bacteria, not human cells.

A phage attaches to a susceptible bacterium, injects its genetic material, and turns the bacterial cell into what Van Tyne describes as “a phage factory.” Once enough new phages are produced, the bacterium bursts open, releasing more phages that can attack neighboring bacteria.

“It’s that cell death part of the phage life cycle that we’re really interested in when we think about using phages for therapy,” she said.

The word “phage” itself comes from the Greek word phagein, meaning “to eat”— an apt description for viruses that essentially consume bacteria from the inside out.

A Personalized Approach

Unlike many antibiotics, which can target a broad range of bacteria, phages are remarkably specific. A phage that destroys one bacterial strain may have no effect on another.

That specificity makes developing treatments both exciting and challenging.

“I like to tell people that we’re basically matchmakers,” Van Tyne said. “A doctor refers a patient to us, we obtain the bacteria causing that patient’s infection, and then we test it against phages that we’ve collected and characterized to see if we have a match.”

The Pittsburgh Phage Program maintains libraries of phages that can be screened against bacteria from individual patients. If researchers identify an effective match, the phages may be used to treat patients with multidrug-resistant infections through compassionate use or clinical trials.

Currently, the program most often receives requests for patients infected with Pseudomonas aeruginosa, a bacterium responsible for severe pneumonia, bloodstream infections, and other difficult-to-treat illnesses. Although Pseudomonas represents just one member of the group of highly resistant bacteria known as the ESKAPE pathogens, it has become the initial focus of the new NIH-funded center because of its frequency and clinical impact.

From Personalized Treatment to Standard Practice

While phage therapy has shown promise, today’s process is highly individualized. “The way that we do phage therapy now is literally patient by patient,” Van Tyne said. “It’s the epitome of personalized medicine.”

That approach, however, is difficult to scale. Researchers still need better answers to fundamental questions, including how much phage should be administered, how often treatments should be given, the best routes of delivery, and how long therapy should continue.

Those are precisely the questions the new P01 grant is designed to address.

Working alongside collaborators from the University of Southern California, Walter Reed Army Institute of Research, Florida International University, and industry partner Intralytix, investigators will develop standardized tools to optimize phage selection, dosing strategies, and preclinical testing. The long-term goal is to make phage therapy more predictable, reproducible, and accessible for patients who need it.

Learning from Patients

One reason Pitt is uniquely positioned to lead this effort is its established compassionate use phage therapy program.

“We have this unique opportunity to study what happens to human patients when we give them phage therapy,” Van Tyne said.

Rather than relying solely on laboratory or animal models, researchers can study how phages move through the human body, how bacteria respond, and whether patients improve clinically. Those insights help inform future treatments while building the evidence needed to move the field forward.

Van Tyne’s own interest in phage therapy began about a decade ago after learning about a widely publicized case in which physicians successfully used experimental phages to treat a professor with a life-threatening multidrug-resistant infection. Watching researchers bring phages “literally out of the laboratory and into the clinic,” she said, inspired her to help build a similar program at Pitt.

Looking Beyond Antibiotics

Van Tyne believes medicine is entering a pivotal moment. “I think we’re rapidly approaching a post-antibiotic era,” she said. “For some patients, they’re already living that reality today.”

She doesn’t see phages as replacements for antibiotics, but as an important new addition to physicians’ treatment options.

“I’m really excited about the possibility of using phages as a new tool in the antibiotic armamentarium—to add another tool to the toolbox available to doctors to treat patients with infections that are right now very difficult to treat.”

The new NIH investment reflects growing national recognition that phage therapy deserves serious scientific attention. “I think there’s a renaissance happening right now,” Van Tyne said. “When a major organization like NIH is willing to invest in understanding how best to use this therapy, it signals a real commitment to developing phage therapy for the future.”

For patients facing infections that no longer respond to antibiotics, that future cannot come soon enough.