CM – Trained viruses are found to be more effective in fighting antibiotic resistance


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June 7, 2021

by Mario Aguilera, University of California – San Diego

The threat of antibiotic resistance increases as bacteria continually evolve to thwart even the most effective modern drug treatments. By 2050, more than 10 million human lives are threatened by antibiotic-resistant bacteria, as existing therapies prove to be ineffective.

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Bacteriophages or « phages » have become a new source of hope against growing antibiotic resistance. Ignored by western science for decades, phages are the subject of increasing research attention due to their ability to infect and kill bacterial threats.

A new project led by Joshua Borin, a graduate of the University of California San Diego Biological Sciences, a Member of the laboratory of Associate Professor Justin Meyer, has proven that phages that undergo special evolutionary training increase their ability to suppress bacteria. Like a boxer training before a title fight, pre-trained phages have shown that they can delay the onset of bacterial resistance.

The study, which included contributions from researchers from the University of Haifa in Israel and the University of Texas at Austin, will be released on Aug. Published June 6 in the Proceedings of the National Academy of Sciences.

« Antibiotic resistance is inherently an evolutionary problem, so this paper describes a possible new solution as we run out of antibiotic options, » said Borin. “Using bacterial viruses that can adapt and evolve to the host bacteria that are supposed to infect and kill them is an old idea that is being revived. It is the idea that the enemy of our enemy is our friend. ”

The idea of ​​fighting bacterial infections with phages goes back to before World War II. But when antibiotics became the leading treatment for bacterial infections, research into phage for therapeutic potential was largely forgotten. That mindset has changed in recent years as deadly bacteria evolve and render many modern drugs ineffective.

Borin’s project was designed to train specialized phages to fight bacteria before they hit their ultimate bacterial target . The study, carried out in laboratory bottles, showed classic mechanisms of evolution and adaptation. The bacteria, Meyer said, moved predictably to counter the phage attack. The difference was in the preparation. According to the study, phages trained for 28 days were able to suppress bacteria 1,000 times more effectively and three to eight times longer than untrained phages.

« The trained phage had already experienced how the bacteria tried to evade it, » says Meyer . “It had ‘learned’ in the genetic sense. It had already developed mutations to counteract the movements of the bacteria. We use the phage’s own improvement algorithm, evolution through natural selection, to regain its therapeutic potential and to solve the problem. « Of bacteria that develop resistance to further therapy. »

The researchers are now expanding their results, to study how pretrained phage work on bacteria important in clinical settings, such as E. coli. They are also working to evaluate how well training methods work in animal models.

UC San Diego is a leader in phage research and clinical applications. In 2018, the University’s School of Medicine established the Center for Innovative Phage Applications and Therapeutics, the first dedicated phage therapy center in North America.

« We have prioritized antibiotics since they were developed and now that they are becoming less and less useful are, people resort to phage to use as a therapeutic, « said Meyer. » M Either of us investigate conducting the experiments necessary to understand the types of procedures and processes that phage therapeutics can improve.  »

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