Are Phages the Wave of the Future? Using Viruses to Treat Bacterial Diseases

Researchers with the University of Pittsburgh in Pennsylvania used a genetically modified bacteriophage—a type of virus that infects bacteria—to successfully treat 15-year-old Isabelle Carnell-Holdaway, a British girl with cystic fibrosis who had been fighting a drug-resistant Mycobacterium abscessus infection half her life. Her physician, Helen Spencer, with London’s Great Ormond Street Hospital, was out of options and reached out to Graham Hatfull at U of P.

Their approach appeared to work, although they caution that because it was outside a controlled clinical trial, there may be other factors to their patient-specific cocktail. She continues to receive the treatments, which haven’t cured the infection, but appears to have it under control. The research was published in the journal Nature Medicine.

Earlier this year, Ella Balasa, a 26-year-old from Richmond, Virginia, made the news when she was apparently successfully treated for a lung infection using a bacteriophage. Balasa has cystic fibrosis, which she was diagnosed with at the age of one year.

A bacteriophage is a virus that infects bacteria. They aren’t typically used to treat bacterial infections, but in desperate cases, they have been used to treat particularly antibiotic-resistant infections. Such as the one that Balasa was battling.

As of April 2019, Balasa, by her own account, appears to be doing fine. At the time of the infection, her lung function was at 18%.

Bacteriophages were discovered independently by Frederick Twort in 1915 and Felix d’Herelle in 1917—a full decade before the discovery of penicillin. At that time, they were used to treat dysentery and cholera. But timing is important, and not much was known about viruses and phages at the time—it would be another 25 years, in 1940, before an image of a phage was made using an electron microscope.

And unlike broad-screen antibiotics, strains of phage are specific to strains of bacteria. A broad-screen antibiotic can be used to treat a range of bacterial infections, but phages need to be chosen and purified specific to the infecting bacteria.

On the other hand, as antibiotic-resistance becomes a bigger issue and development of new antibiotics is slow, attention is turning toward the possibilities of phages to treat antibiotic-resistant bacteria. A 2017 article by Veerasak Srisuknimit on the Harvard University blog, wrote, “Now that more and more bacteria have developed resistance to antibiotics, scientists around the world have a renewed interest in phages. The European Union invested 5 million euros in Phagoburn, a project that studies the use of phages to prevent skin infections in burn victims. In the USA, the FDA approved ListShield, a food addictive containing phages, that kills Listeria monocytogenes, one of the most virulent foodborne pathogens and one cause of meningitis. Currently, many clinical trials using phage to treat or prevent bacterial infections such as tuberculosis and MRSA are undergoing.”

Although a long way from being widespread, and in the cases described above, they were conducted outside controlled clinical trials, there is increased interest in how phages might be exploited to treat antibiotic-resistant bacterial infections. One of the aspects of phages that is intriguing—and maybe a little disgusting—is where they are found. In the case of Isabelle Carnell-Holdaway, the phage was scraped from the bottom of a rotten eggplant. Vox notes, “Phages … are often found in really dirty places. Ditches. Ponds. Sewage.”

So researchers are creating phage libraries, traveling the world to collect new viruses and store them. The University of Pittsburg has a library of more than 10,000 different viruses. Isabelle Carnell-Holdaway received a cocktail of three phages. The one from the eggplant was collected in South Africa in 2010. The two others were found in the U.S. and were genetically engineered to more effectively kill her bacteria.

Now 17 years old, Carnell-Holdaway is recovering, but not exactly cured. In a May 2019 story by CNN, Spencer said, “We haven’t cured her.” The bacterium still causes skin lesions “on occasion. I hope with time, eventually, she’ll clear the infection. If it will happen or not, I don’t know.”

One reason science is returning to the study of phages is because of modern gene sequencing technology. Screening the viruses is cheaper and easier and faster, and there’s a better understanding of the biology and pharmacology of phages. Some major companies, such as Johnson & Johnson, are investing in potential phage therapeutics, but there are challenges related to production costs and our understanding of phage biology is still very early.