Phages to the rescue? Pitt lab develops viruses to combat antibiotic-resistant bacteria

Bacteria-killing viruses built from scratch in a University of Pittsburgh lab could be a breakthrough in the battle against fearsome antibiotic-resistant infections.

Pitt biotechnology researcher Graham Hatfull spearheaded the development of the viruses made entirely of synthetic genetic material in a study set for publication this week in the Proceedings of the National Academy of Sciences.

California-based Ansa Biotechologies was tapped to create the genetic material and New England Biolabs to arrange it into functioning bacteriophages, or just phages, as the viruses are often called.

The exact phages created in the study attack pathogens causing tuberculosis, leprosy and other illnesses. But the real breakthrough here is the promise of creating an infinite number of phages from the ground up.

“It opens the door to be able to design, invent, engineer phages in pretty much any way that we choose to do so,” Hatfull told TribLive on Monday.

Phages are harmless to humans. In fact, our bodies are full of these microscopic agents, which outnumber all other life on earth combined.

But they’re something of bacteria assassins, offering a targeted way to take out stubborn pathogens that have evolved defenses against the relatively blunt tool of antibiotics.

Phages have been of scientific interest for more than 100 years. But in practice, they remain a niche, last resort treatment far removed from the sophistication of 21st century medicine, according to Hatfull.

Most phages used in medicine are cultured and purified in a lab. They’re approved by the federal Food and Drug Administration for use in patients who’ve exhausted all other avenues.

Pleas from doctors come in every few days, said Hatfull, whose lab also makes phages the old-fashioned way. He has produced and sent phages to help some 50 patients for whom antibiotics have proved ineffective.

There have been a few hundred cases, though, where his lab simply doesn’t have the right virus available. Gene editing removes this limitation, and can even allow scientists to dream up phages that don’t exist in nature but may be highly effective at taking out certain harmful bacteria.

Phages, which vary greatly in shape and size but tend to have a lunar lander look to them, have about 100 genes, more than half of which are poorly understood, according to Hatfull.

In a 2022 study involving Hatfull, 11 of 15 patients who received phages saw clinical improvement. There is little evidence, he said, of any serious side effects, unlike those caused by antibiotics.

“They’re really not foreign objects to us in the same way that many antibiotics are,” Hatfull said. “You can think of antibiotics as being chemicals, and chemicals are often quite nasty and toxic.”

Phages are incredibly species-specific in their hosts, with some able to infect only a single type of bacteria. But once they’ve found a susceptible victim, they get to work like any other virus by hijacking the host cell’s resources to replicate.

When the host cell dies, the new phages are released to repeat the cycle.

The precision and apparent safety of phages make them a popular bet to turn the tide on antibiotic-resistant bacteria, a pressing concerns for many public health experts.

In 2023, roughly 1 in 6 infections tested by labs worldwide were resistant to antibiotics, according to a report from the World Health Organization.

Nearly 40% of antibiotics used to treat common blood, gut, urinary and sexually transmitted infections lost effectiveness in the five years leading up to the report.

When antibiotics fail, what were once highly treatable infections can spiral out of control.

The World Health Organization estimates antibiotic-resistant bacteria kills about 1.2 million people each year. Lower-income countries are hit hardest, but the Centers for Disease Control and Prevention counts about 35,000 annual deaths in the U.S. from these challenging infections.

Hatfull is hopeful his process can be scaled up to make a dent in those grim figures.

“I would see this paper and what we described there as a kind of a proof of concept,” Hatfull said. “Now the challenge is to see how we can best put that to good usage.”