Phage therapy in traumatology

Bacterial infection was cured by a virus

Kirill Stasevich, Science and Life (nkj.ru )

One of the victims of the 2016 terrorist attacks in Brussels was a woman with a fractured hip and other injuries. The fracture was temporarily stabilized for her to heal other wounds and then return to the broken bone again, but, unfortunately, the Klebsiella pneumoniae bacterium got into her leg, in the form of two well-known strains with broad resistance to antibiotics. Doctors experimented with different treatment regimens for several months, but it was impossible to get rid of the bacterium — it remained in the wound, preventing the bones from fusing.

K. pneumoniae forms biofilms — the so-called colonies of bacteria connected by an intercellular matrix. It consists of various bacterial substances that make the colony very strong in a mechanical sense and insensitive to drugs that penetrate the matrix extremely poorly. In addition, K.pneumoniae bacteria, in case of a drug threat, sink into an inactive, dormant state, and antibiotics act only on "awake" bacteria that have an active metabolism. Dormant bacteria are just waiting for the antibiotic to disappear in order to wake up and start harming again.

The doctors who dealt with the patient with the fracture realized that non-standard treatment was needed, and decided to set a virus on the bacterium. In fact, phage therapy ("phago-" — because bacteriophages are used here, that is, viruses that infect bacteria) — this is a rather old method, originating in the first half of the last century, only now it is gaining popularity again due to the spread of bacteria insensitive to antibiotics. The necessary bacteriophage was taken at the Tbilisi Institute of Bacteriophages, Microbiology and Virology. Eliava. Moreover, the virus was not immediately injected into the wound, but was given to train on Klebsiella in laboratory conditions. The virus gradually got used to the bacteria — that is, mutations appeared in it generation after generation, which allowed it to infect K. as efficiently as possible. pneumoniae. In the end, the researchers had a strain of the virus with sufficient therapeutic potential in their hands.

In February 2018, 702 days after the injury, the patient was transplanted with a bone implant supplemented with an antibiotic and a virus. More precisely, the antibiotic and the virus were injected into the wound through a special catheter for six days, and after two days it became clear that things were going well. The infection disappeared, the bone healed, and after three months the woman began to walk as before. Treatment details are described in an article in Nature Communications (Eskenazi et al., Combination of pre-adapted bacteriophage therapy and antibiotics for treatment of fracture-related infection due to pandrug-resistant Klebsiella pneumonia).

Bacteria also have antiviral protection, and they can improve it over time. However, they do not develop resistance to viruses as quickly as to antibiotics — for example, different bacteria cannot exchange phage resistance genes, as they do with antibiotic resistance genes. In addition, viruses also evolve, and in the laboratory you can quickly get a new strain of virus trained to infect a phage-resistant bacterium. So it can be assumed that there will be more and more such examples when a prolonged bacterial infection has been cured by a viral one.

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