A ‘library’ of bacteria-killing viruses: Harnessing the power of phages

An estimated 38 trillion bacteria live in the human body—and only a small fraction are harmful to our health. However, the harmful ones can cause serious illness, especially when they develop resistance to antibiotics.

To overcome drug resistance and fight severe, hard-to-treat infections, researchers are turning to a type of virus found in nature that infects only bacteria: bacteriophages, or “phages” for short.

A team of University of Colorado Anschutz School of Medicine researchers has spent the last 15 years compiling a library of phages to target especially stubborn bacteria that naturally live in the intestines.

“Phages have been used historically for decades as tools to understand molecular biology, but there’s been a resurgence in interest in them due to the rising incidence of antibiotic-resistant bacterial infections,” says Breck Duerkop, Ph.D., associate professor in the Department of Immunology & Microbiology. “We can isolate viruses against infections that are difficult to treat, and some of the viruses will kill the bacteria very readily.”

How viruses work—and how Duerkop’s team isolates them

Just like human cells, bacterial cells can be infected by viruses. Duerkop says nearly all bacteria have viruses that infect them, so phages are found in practically any environment where bacteria live. Viruses generally aren’t considered living things, but they contain genetic material (DNA or RNA), and they can use host cells to make copies of themselves.

In human cells, according to the National Human Genome Research Institute, a virus gets inside a host cell by binding to a receptor on the cell surface, much like a key unlocking a door. Once inside, DNA or RNA from virus particles takes over cellular functioning and uses materials in the cell to create more virus particles, which can then infect other cells. Viruses disrupt cell activity and damage their host cells, sometimes killing them.

Phages can poke holes through cell walls and inject genetic material directly into bacterial cells. Importantly, phages can’t infect human cells, but they can cause similar damage inside bacterial cells as other viruses do in human cells.

Duerkop’s research group finds and isolates phages to study how they kill bacteria, how bacteria may become resistant to them, and how the phages can be combined with FDA-approved drugs to treat people with serious bacterial infections.

These researchers are especially interested in treatment-resistant bacteria. They primarily study Enterococcus faecalis and Enterococcus faecium, two highly drug-resistant bacterial species that normally live in the human gut without causing problems but can cause severe infections, especially in people with compromised immunity.

Other antibiotic-resistant bacteria, including emerging pathogens like Enterobacter hormaechei and Klebsiella oxytoca, have also piqued the team’s interest.

To find the right phages, the team gathers viruses from untreated wastewater, which contains these and other types of bacteria that make up the gut microbiome. After exposing the bacteria they’re trying to target to the wastewater, the researchers grow the bacteria on agar plates (known as bacterial lawns). They wait a little while, then extract phages directly from the round plaques that form within the bacterial lawns.

From there, the team uses a centrifuge to purify the phage samples and stores the phages in buffers in the refrigerator, where they are stable and have long shelf lives.

Duerkop says he aims to keep a variety of phages on hand that can infect the bacteria his team is interested in. His team currently has more than 30 different viruses that infect enterococcal bacteria and roughly 15 to 20 that infect Enterobacter and Klebsiella.

“The idea of generating a library is you want some diversity,” says Duerkop. “Not every phage infects every type of bacteria. They’re very specific.” Phages can broadly infect strains of a particular bacterial species or be specific to a single strain, making them very precise.

A promising treatment for infections

Phages have shown promise as a treatment for these types of infections. They can be combined with standard antibiotics and delivered orally or directly into the bloodstream via an IV, especially if the patient has a blood infection (septicemia). Phages have even been used topically to treat infected burns and other skin injuries.

Phages aren’t a cure-all, and bacteria can develop resistance to the phages themselves, but they can be an effective option when traditional antibiotics aren’t working on their own. Duerkop says antibiotic-resistant bacterial infections aren’t going away anytime soon, so it’s essential to continue researching what phages can do.

“It’s imperative that we explore creative ways to use phages in combination with antibiotics to target antibiotic-resistant bacteria,” says Duerkop.

“We are just beginning to scratch the surface on the diversity of phages that have therapeutic potential. By continuing to study the biology of these phages, we stand to learn more about our natural world and the role of phages in it.”

Who’s behind this story?

Sadie Harley

BSc Life Sciences & Ecology. Microbiology lab background with pharmaceutical news experience in oil, gas, and renewable industries.

Full profile →

Andrew Zinin

Master’s in physics with research experience. Long-time science news enthusiast. Plays key role in Science X’s editorial success.

Full profile →