Atomic structural model of bacteriophage T4 in UCSF Chimera software using pdbs of the individual proteins. Credit: Victor Padilla-Sanchez, Ph.D.
In 2018, scientists for the first time, genetically engineered bacteriophages to treat a widespread, antibiotic-resistant Mycobacterial abscessus infection in a 15-year-old cystic fibrosis patient with a double lung transplant. Now, they have taken a step further—using the bacteriophages to treat a similar lung infection in order to clear the way for another cystic fibrosis patient to receive a life-saving lung transplant.
Twenty-six-year-old Jarrod Johnson suffered repeated lung infections throughout his life. As an adult, he experienced a rapid decline in his lung function following a persistent Mycobacterium abscessus infection over a six-year period. By 2020, his lung function had fallen below 30%. Johnson needed a lung transplant to live more than a few years, but he had been refused by three transplant centers because of his mycobacterial infection. So, his doctors turned to bacteriophages to clear his infection and pave the way to a transplant.
After much interest abroad, especially in Russia, phage therapy, the therapeutic use of bacteriophages for the treatment of pathogenic bacterial infections, finally began to gain momentum in the U.S. in the early 1940s. The technique was short-lived, however, as penicillin was successfully purified in 1942 and large-scale production of the antibiotic was possible by 1944—rendering phage therapy unnecessary. But now, as antimicrobial resistance continues to worsen around the world and scientists look for alternatives, once-obsolete phage therapy could become more critical than ever.
Treatment plan
In 2016, Johnson’s doctor, Jerry Nick, MD, sent samples of the Mycobacterium abscessus from Johnson’s lungs to Graham Hatfull, a professor at the University of Pittsburgh who pioneered that first successful bacteriophage treatment in 2018.
Since phages are specific for only a few types of bacteria, therapy only works when utilizing the phage that can kill the specific infection strain. Luckily, as the foremost expert in bacteriophages, Hatfull’s lab has one of the largest banks of phages in the country with a collection of 15,000 individual phage isolates and DNA sequences for roughly a fifth of them.
In Johnson’s case, Hatfull and his team screened dozens of phage candidates, ultimately identifying two that efficiently killed the mycobacterium infecting his lungs. They then genetically engineered the phages to optimize their potential.
Johnson received his first infusion of phages in September 2020, followed by 500 days of twice-daily infusions. According to the paper published in Cell, within two months, a variety of genomic, cell culture and clinical markers indicated that the treatment was succeeding. Just over a year after the phage treatment began, Johnson’s infection cleared—making it safe to place him on the active transplant list.
He received a lung transplant in October 2021, remaining on phage therapy throughout the procedure as well as during his recovery. Again, a range of markers indicated no evidence of infection following the transplant. Now, in 2022, Johnson has discontinued all treatment for Mycobacterium abscessus and is living a normal life.
“This research can serve as a roadmap for future use of phages to treat patients with severe Mycobacterium abscessus lung infection and to save lives,” said Nick.
With multiple successful case studies now, the scientists say they hope to see the use of phages to treat a broader spectrum of patients, helping determine the roles of antibodies and phage resistance in this treatment option.