Infectious Diseases

Trained viruses wipe out bacterial infections by anticipating evolution

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Bacteriophages are viruses that prey on bacteria, making them good candidates for treatments against superbugs
Phages, both trained and untrained, are pitted against bacteria in flasks in the lab
UC San Diego
Red and white markers indicate bacteria that have survived the treatment, allowing researchers to tally up the effectiveness of the phage treatment
UC San Diego
Bacteriophages are viruses that prey on bacteria, making them good candidates for treatments against superbugs
View gallery - 3 images

Bacteria have a nasty ability to rapidly evolve, allowing them to evade antibiotics in short order. But now, scientists at UC San Diego have used evolution against them, by “training” bacteria-killing viruses to anticipate their next moves.

When lifeforms are exposed to stressful conditions, some individuals will survive better than others, thanks to random genetic mutations that bestow helpful traits. Over time, those traits will end up spreading across a population until it becomes the norm. That’s evolution at work, and usually it’s a wonderful process for helping life persist in the face of adversity – but there are actually times when we’d rather root for adversity.

Bacteria are some of nature’s most prolific evolvers, able to not just pass useful genes down to the next generation but actually swap them like trading cards within a current generation. So when they’re faced with the harsh environment of antibiotics, it’s no wonder they’ve managed to evolve their way out of danger within a few decades.

As our best drugs begin to fail, bacteria are poised to become one of the most pressing public health concerns in the near future. So scientists are increasingly looking to a long-ignored alternative – phage treatment.

Bacteriophages (or just phages) are viruses that specifically prey on bacteria, and while they were an early subject of study in treating bacterial infections, the development of antibiotics soon took medical science down another path. But now, with that path seemingly reaching a dead end, phages are looking promising once again.

Phages, both trained and untrained, are pitted against bacteria in flasks in the lab
UC San Diego

In the new study, the researchers set out to train phages to be better bacteria killers. The phages were grown in flasks alongside their target bacteria for 28 days, so that they co-evolve and essentially learn the evolutionary escape routes that the bacteria might try to use.

Then, these trained phages were set loose on other populations of the bacteria. And sure enough, they were much better equipped to take out the targets, suppressing bacteria around 1,000 times more effectively than the untrained phages. The effects lasted between three and eight times longer, too.

“The trained phage had already experienced ways that the bacteria would try to dodge it,” says Justin Meyer, lead author of the study. “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.”

Red and white markers indicate bacteria that have survived the treatment, allowing researchers to tally up the effectiveness of the phage treatment
UC San Diego

The study adds further evidence to support the use of phage therapy to treat bacterial infections. A few years ago a phage treatment was given to a human patient with a dangerous infection for the first time, which might have saved her life. And they don’t even necessarily need to kill the bacteria to work – other studies have shown that they might just distract the bugs and make antibiotics effective again.

The research was published in the journal Proceedings of the National Academy of Sciences.

Source: UC San Diego

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2 comments
Kiffit
Bacteriophage therapy found its most potent expression behind the Iron Curtain after borrowing the idea from WW1 experiments and treatment regimes for the wounded on the western front. Phage therapy was widely used by Soviet military medicos during WW2 and because of the impermiability of the 'Iron Curtain', antibiotics did not overwhelme phage therapy in the way it did in the west.

I have a Ukrainian relative who explained to me that it was still being used right up to the end of the Soviet regime.

It is a much more labor intensive process than using anti-biotics, because the phages have to be personalized and grown from the patient. And obviously, the treatment regime is much slower. Patients just have to suffer while they wait for their dose to grow.....
Karmudjun
This is old therapy whose limits have not been explored either in the USA or in the old USSR. Rapid development of the necessary useful phages has yet to occur - possibly the technological advances of the recent past - the kind of accelerated medical research resulting in RNA virus development might apply to phage research. When it comes to orthopedic surgery, we need an anti-bacterial treatment that can go all the places the bacteria go and fight them in the bone marrow and muscle tissues. Even the "flesh eating bacteria", ie. antibiotic resistant bacteria that just keep doing what they evolved to do - would benefit from phage therapy - but there is no timeline for "training" phages under those circumstances. It has to happen immediately - it has to be applicable in emergencies! That day may come. I hope so.