Using a Virus to Beat Bacteria

Antimicrobial resistance is a growing threat, one that health officials say could lead to 10 million deaths by 2050. It’s a scenario that makes discovering new ways to combat drug-resistant infections critical.

A researcher at the University at Buffalo is investigating what he sees as the battle’s next frontier: bacteriophages—a type of virus that infects bacteria but not human cells. With many unanswered questions as to how these phages work in the body, however, their use at this point is largely experimental.

With a $3.6 million research grant from the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, Nicholas Smith, assistant professor of pharmacy practice, is working to change that. Over the next five years, Smith and his team will investigate how phages distribute throughout the body to the site of infection and how effective they are in resolving infections once there. They also aim to determine the best strategy to combine multiple phages into more powerful cocktails.

Phages are nothing new—they were actually discovered in the early 20th century. Phages were overlooked, Smith explained, because other solutions for subduing bacteria, such as penicillin, were highly effective and more predictable.

“Now that we’re facing all this resistance to antibiotics, the research community has started to revisit phages as a potential alternative,” he said. “In our study, we’re trying to apply a lot of the tools for drug development that have come into existence since phages were originally discovered.”

Currently, phages are predominately administered only in compassionate use circumstances—for patients who would likely die without treatment and for whom there are no other options, Smith said.

He and his team are looking at phages that have demonstrated clinical success in these cases to determine what level of distribution equates to an effective dose.

The first phase of the research, already in progress, concerns picking individual phages and combining them for optimum results. The second and third phases will be devoted to developing the cocktails and testing optimal combinations. The final phase is setting up the infrastructure for future human trials.

Smith said that they will conduct experiments using in vitro cell cultures, as well as some computer model-based approaches.

“The urgency of finding new ways to combat drug-resistant infections, especially for our most vulnerable patients, drives everyone on the team,” he said.