Threat of Antibiotic Resistance a Shot in the Arm for Phage Research

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Yale University last month launched the Center for Phage Biology and Therapy, a new endeavor to advance research into using viruses to address the growing concern about antibiotic-resistant bacteria.

Since the first antibiotics were discovered nearly a century ago, bacteria-killing medicines have revolutionized humanity’s ability to combat bacterial infections. However, as antibiotics have become more widely used, more and more bacteria are evolving resistance to them.

Antibiotic-resistant bacteria are especially a concern in cystic fibrosis (CF), where thick mucus in the lungs provides a fertile breeding ground for infectious bacteria.

The growing resistance to antibiotics is a “sobering reminder that not too far off in the future, the expected rates of death from antimicrobial resistance in the human population around the world may exceed the rates of deaths from common diseases, such as cancer,” Paul Turner, PhD, director of Yale’s new center, said in a press release.

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The Center for Phage Biology and Therapy wants to promote research into the use of lytic phages — viruses that can infect and kill bacteria. The idea is basically to infect the infector, using phages instead of antibiotics to kill the bacteria.

The center formalizes collaborations at Yale that have been ongoing since 2016, when a case of antibiotic-resistant Pseudomonas aeruginosa (the main bacterial agent in CF lung infections) was successfully treated using a phage discovered in a sample of pond water.

“At Yale, we have had successful therapeutic use of lytic phages,” Turner said.

The center is making a multi-million-dollar investment in phage biology research and phage applications in CF as well as other indications where resistant bacteria can cause problems, such as sepsis, prosthetic-joint infections, and post-COVID-19 pneumonia.

Among other projects, Yale researchers are conducting a Phase 1/2 clinical trial, called CYPHY (CYstic Fibrosis BacterioPHage Study at Yale; NCT04684641), to test phage therapy in adults with CF who have chronic P. aeruginosa airway infections. Early data, presented late last year, indicated that phage therapy could improve patients’ lung function.

The CYPHY trial “is an exemplar of using our strategy of looking more towards treating patients chronically over the long term with phages to see if we can affect their multi-drug resistant infections and see clinical improvements,” Jon Koff, MD, the trial’s principal investigator, said.

CYPHY is actively recruiting participants at Yale, and funding is available to help select patients with travel and lodging.

“The trial has been very rewarding and a great opportunity for me to engage with our patients, our community, and providers around the country,” Koff said. “We’ve seen patients come to Yale from all over and this has allowed me to communicate to folks from multiple communities about our phage and our phage strategies.”

Ella Balasa, a writer, scientist, and CF patient advocate, received phage therapy at Yale in 2019 to treat an antibiotic-resistant lung infection. Balasa recalled her lung function was about 20% before she was treated, but phage therapy “did clear my infection,” she said.

“I want everyone to know that this therapy can be a viable option for antimicrobial resistance. I am excited that there are groups like [Yale] that are bringing clinical trials to people,” Balasa said.

“I believe that without [phage therapy], at this point, I would have been transplanted because of the severe lung infection that I was facing at the time,” she said.

January’s launch event featured a panel discussion about the documentary “Salt In My Soul.” The 96-minute film chronicles the life of Mallory Smith, a woman with CF who tried the experimental phage therapy, but ultimately died at age 25 from an infection in her newly transplanted lungs.

“Mallory was willing to try phage therapy. We had many, many long talks about it,” said her mother, Diane Shader-Smith. “I think the main reason that people love the film, despite the tragedy, is that they leave feeling hopeful. And phage therapy is that hope.”

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