A novel project has unveiled two discoveries that widen the potential and our understanding of bacteriophages. Joshua Borin, a graduate student of the University of California San Diego Biological Sciences and a member of Associate Professor Justin Meyer’s laboratory, led a project that first uncovered the ability of training bacteriophages. Secondly, has seen that such trained bacteriophages have shown effectiveness against antibiotic resistant bacteria.
The study, which included contributions from researchers at the University of Haifa in Israel and the University of Texas at Austin focused on discovering the evidence that bacteriophages, like many other organisms, are capable of undergoing special evolutionary training. Such training would increase their capacity to subdue their bacterial target. The project focused on training the bacteriophages, prior to them encountering their bacterial target.
“Antibiotic resistance is inherently an evolutionary problem, so this paper describes a possible new solution as we run out of antibiotic drug options,” said Borin. “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.”
Trained bacteriophage against antibiotic resistant bacteria
Conducted in laboratory flasks, the study demonstrated the classical evolutionary and adaptational mechanisms. The bacteria moved predictably to counter the phage attack; however, the difference was in preparation. The bacteriophage had been trained for 28 days and showed the ability to suppress the bacteria 1,000 times more effectively and 3 to 8 times longer than the untrained bacteriophages.
“The trained phage had already experienced ways that the bacteria would try to dodge it,” said Meyer. “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.”
The researchers are now extending their findings to research the performance of the pre-trained bacteriophages against bacteria in clinical settings; such as; Escherichia coli, as well as evaluating how well the training methods work in animal models.
UC San Diego has been a leader in phage research and clinical applications. The university’s School of Medicine established the Center of Innovative Phage Applications and Therapeutics back in 2018 and it Has been 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 people are looking back to phage to use as therapeutics,” said Meyer. “More of us are looking into actually running the experiments necessary to understand the types of procedures and processes that can improve phage therapeutics.”