In a first, engineered bacteriophages, cure teen battling microbial infection

Bacteriophages have often been used for its capacity to attack and destroy bacteria.

Scientists from US and Britain successfully curbed a serious infection caused by a multidrug-resistant (MDR) mycobacterium Mycobacterium abscessus using genetically engineered bacteriophages. While bacteriophages have often been used for its capacity to attack and destroy bacteria, it is the first time that genetically engineered phages were employed as a final course of action in medical treatment procedure.

The treatment was carried out on 15-year-old Isabelle Carnell-Holdaway.

Over 7 months three bacteriophages, named Muddy, ZoeJ,and BPs, were selected and isolated to make the cocktail which largely cured the patient after being administered for about 6 months. The bacteriophages were selected from a library of more than 15,000 phages by scientists at the University of Pittsburgh.

Graham Hatfull, PhD, a professor of biological sciences at the University of Pittsburgh, and James Soothill, MD, a microbiologist at London's Great Ormond Street Hospital, were the ones to initiate the treatment procedure.

Carnell-Holdaway developed the microbial infection after a double lung transplantation at a London hospital in 2017. However, the already present non-tuberculosis mycobacteria resurfaced after the surgery and with the antibiotics not working and her body immunity suppressed by immunosuppressive drugs (given to prevent rejection of the new lungs), the infection spread throughout her body causing skin lesions on her limbs.

In quest for alternative treatment

With no method to successfully curb the infection, Soothill contacted Graham Hatfull, PhD, Professor of Biological Sciences at the University of Toronto, to chart out a probable course in phage therapy. With his curiosity aroused by the profiles of the patient, Hatfull set about choosing the right phage that would affect the particular bacterial strain of the particular patient. Of the three strains discovered as lethal to the concerned bacterium, Muddy proved to be the best for the task. The other two strains were engineered to make them more efficient.

Both the experts were not confident of succeeding at the task. Yet their curiosity was aroused and wanted to see it as a research question. The Howard Hughes Medical Institute's SEA-PHAGES* database, compiled by Hartfull over three decades, proved to be the source for the phages. The phages were tested, multiplied, amplified and the cocktail was tested for toxins before IV use.

Led by Helen Spencer, MD, clinicians in London did a topical test in June 2018 on Carnell-Holdaway's incision and was followed by IV therapy the next day. With no signs of any adverse effects, the treatment was continued at home after her discharge.

New possibilities

Scientists are hopeful that phage therapy may be used to treat tuberculosis.

While it is difficult to have a generalisable therapy due to the specificity of each phage, yet they can be preferred tools as they do not cause side effects unlike antibiotics (which can lead to the growth of multidrug resistant variants or even remove beneficial bacteria) and is low on toxicity and leave human cells unharmed.

Steffanie Strathdee, PhD, co-director of the Center for Innovative Phage Applications and Therapeutics (IPATH), at the UC San Diego School of Medicine in La Jolla, US opines that with genetically altered phages a possibility, it may be possible to engineer phages that attack multiple strains of bacterial species.

Scientists look forward to further research in tapping the great potential of phage therapy.

* Science Education Alliance - Phage Hunters Advancing Genomics and Evolutionary Science.

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