Israeli scientists have developed ‘spot’ viruses that kill gut-damaging bacteria

Israeli scientists are working on the development of a “precision weapon” against intestinal diseases, consisting of viruses that fight bacteria.

Two different virus “cocktails” are in Phase 1 clinical trials, with early results showing they are safe, and extensive in vitro and animal tests showing they fight the bacteria.

Peer-reviewed research published in the journal Cell shows that the virus effectively reduces the number of Klebsiella pneumoniae bacteria found in large numbers in the intestines of people with Crohn’s and ulcerative colitis.

“To our knowledge, this is a promising approach to precisely suppress the so-called ‘silver bullet’ pathogens without damaging the first shot.” Eran Elinav, an employee of the Weizmann Institute of Science, headed the scientific group.

The idea of ​​using viruses in drugs to fight bacteria, known as bacteriophages or phage therapy, is not new and was intensively studied at the beginning of the 20th century. However, before any significant progress was made, antibiotics were invented and attempts to use viruses in clinical practice were largely abandoned, although scientists continued to use phages in laboratory settings.

Today, there is a resurgence of interest in possible phage therapy due to concerns about antibiotic-resistant bacteria. Some researchers speculate that they may offer a solution to the problem, and several phage therapies are being developed, but none are widely used.

Scientific staff of the Weizmann Institute (from left to right) Dr. Rafael Valdes Mas, Dr. Sara Federici, Prof. Eran Elinav and Dr. Deniz Kwiatsovsky (courtesy of the Weizmann Institute of Science)

The Weizmann project began with scientists analyzing the microbiome of people with Crohn’s and ulcerative colitis to see which bacteria help them fight it.

Dr. Sarah Federici, a member of the research team, told The Times of Israel: “We tested four different people and found that among people with Crohn’s and ulcerative colitis, Klebsiella pneumoniae, the bacteria was present, and we decided to target it with bacterial phages that destroy blood vessels. does not harm cells or other bacteria. In other words, especially with bacteria.

According to Federici, the team “identified viruses or phages that had the potential to fight bacteria and tested them in vitro on the bacteria and then on mice with Crohn’s and ulcerative colitis.” From these results, he said, “We were able to see which viruses were the most effective. We then selected the best viruses and tested them in a laboratory machine that mimics the human gut, and we had good results.

In the latest development, combinations of two viruses – or “cocktails” – were treated in a phase 1 clinical trial. “Study participants received phages for six days and had no adverse reactions,” Federici said. The phages persisted and even multiplied in the human gut over time without causing any unwanted changes to the rest of the gut microbiota, he added.

The phages will now undergo further clinical testing to see if they can fight bacteria and have health benefits.

The Weizmann researchers hope to develop them into drugs that can treat Crohn’s and ulcerative colitis or prevent disease in people diagnosed with high levels of Klebsiella pneumoniae.

“Our vision is to eventually develop personalized therapies for different diseases,” Elinav said, “where the disease-causing strains of gut bacteria are identified in each patient and a phage cocktail is designed to kill only those strains.”

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