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Engineered Phages Treat Drug-resistant Infection

Bacterial infections that can’t be treated successfully with known antibiotics are a serious threat to health. Researchers have been searching for new ways to kill these resistant bacteria. Viruses called bacteriophages, or phages, are one method under study.

Phages prey on bacteria. They infect certain bacteria, replicate inside them, and burst out, killing the bacteria. Dr. Graham F. Hatfull’s research laboratory at the University of Pittsburgh has been building a collection of phages. Over many years, college students in a global science program have isolated more than 10,000 phages from nature.

Dr. Helen Spencer of the Great Ormond Street Hospital in London asked Dr. Hatfull to screen his library for phages that would be effective against the bacterium isolated from a gravely ill teenager. The teen had had a double lung transplant and was out of treatment options after a life-threatening infection had resisted treatment with antibiotics. The Mycobacterium abscessus isolated from the patient’s infection, dubbed GD01, was resistant to all nine antibiotics tested.

The study was funded in part by NIH’s National Institute of General Medical Sciences (NIGMS). Results were reported in Nature Medicine on May 8, 2019.

Testing revealed a phage named Muddy that killed GD01 efficiently. Two other phages, called ZoeJ and BPs, also showed potential. The research team engineered these two phages to be more efficient at killing GD01.

A mixture of the three phages proved effective against GD01 in the lab. Because this mixture showed potential, it was used to soak a gauze pad to lay over the teen’s infected chest wound. The next day, the teen received the mixture intravenously. Every 12 hours, the researchers gave one billion units of the phage mixture.

After one day of treatment, blood tests detected high levels of phages. The high levels suggested that the phages were infecting the bacteria, replicating inside, killing it, and being released into the bloodstream. The research team also detected phages in other body fluids.

After one month of receiving twice-a-day intravenous therapy, the teen began receiving phage-soaked gauze pads on the infected chest wound and numerous skin lesions every day. After 6 weeks of treatment, a PET scan showed that an enlarged lymph node near the liver had shrunk. After six months of treatment, the teen’s chest wound and skin lesions had improved. There were no significant side effects.

“The idea is to use bacteriophages as antibiotics—as something we could use to kill bacteria that cause infection,” Hatfull says. “We purified the phages, we gave them to the patient, and the patient got better.”

M. abscessus strains vary in which phages they are susceptible to, so finding the right phages for each patient will be a challenge. Future research may lead to a phage mixture that works more broadly.

—by Geri Piazza

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