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Trained bacteriophages could help us with our drug resistance issues

If you can't beat them -- hire mercenaries.

Alexandru Micu
June 8, 2021 @ 6:41 pm

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Antibiotic-resistant bacteria are giving our medicine an increasingly-harder time. Bacteriophages however, viruses that prey on bacteria, could help us regain the upper hand.

A bacteriophage model made out of digital Lego blocks. Image credits Pascal / Flickr.

We’re quite spoiled in this modern day and age. Things as minor as cutting a finger are dealt with a wash, bandage, and an antibiotic at most — but they could be very deadly for our ancestors even 100 years ago. But as time passes, bacteria adapt to the drugs they’re exposed to, developing resistance.

It’s estimated that by 2050, antibiotic-resistant bacteria will claim over 10 million lives, as our existing therapies lose effectiveness and patients are left vulnerable.

Bacteria eaters

“Antibiotic resistance is inherently an evolutionary problem, so this paper describes a possible new solution as we run out of antibiotic drug options,” says Joshua Borin, lead author of the study. “Using bacterial viruses that can adapt and evolve to the host bacteria that we want them to infect and kill is an old idea that is being revived. It’s the idea of the enemy of our enemy is our friend.”

Bacteriophages, or phages for short, are viruses that specialize in infecting and reproducing using bacteria. They’re quite like the viruses that make us sick, only with a different ‘meal’ preference.

A new project led by researchers at the University of California San Diego, Biological Sciences department, have shown that phages can be trained, so to speak, to make them better able to attack and destroy bacteria. These pre-trained phages could help delay the onset of antibiotic resistance in groups of bacteria by physically destroying them (rather than chemically, as drugs do), and the team showcases this potential in their experiments. The study also included researchers at the University of Haifa in Israel and the University of Texas at Austin

The experiment was carried out in a series of unassuming laboratory flasks. Boiled down, it involved training specialized phages to recognize and attack certain bacterial strains, in preparation for a final ‘target’. The secret here is that the phages are given an opportunity to better adapt to their prey while kept in the flasks (through natural evolutionary processes). Phages that were ‘trained’ for 28 days, the team explains, were 1,000 times more efficient at suppressing the bacterial colony than untrained ones, and for between three to eight times as long.

“The trained phage had already experienced ways that the bacteria would try to dodge it,” said Associate Professor Justin Meyer, the study’s corresponding author. “It had ‘learned’ in a genetic sense. It had already evolved mutations to help it counteract those moves that the bacteria were taking. We are using phage’s own improvement algorithm, evolution by natural selection, to regain its therapeutic potential and solve the problem of bacteria evolving resistance to yet another therapy.”

While the findings are encouraging, they’re still quite preliminary — more of a proof of concept, if you will. Moving forward, the team wants to test their approach on strains of bacteria important in clinical settings, such as E. coli. Its viability as a treatment option will also be checked using animal models.

The paper “Coevolutionary phage training leads to greater bacterial suppression and delays the evolution of phage resistance” has been published in the journal PNAS.

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