Bacteriophages might one day help solve the growing problem of bacterial infections that are resistant to antibiotic treatment. Researchers at Baylor College of Medicine and the Michael E. DeBakey Veterans Affairs Medical Center have determined that phages can effectively reduce bacterial levels and improve the health of mice that are infected with deadly, antibiotic–resistant bacterial ‘superbugs.’

The study appeared in the journal Scientific Reports.

When bacteria grow out of control, they can enter the blood stream and infect vital organs in the body. The body’s immune system, an army of cells and molecules that fights back infections and other diseases, responds to the bacterial attack, defending the body from the infection. However, the immune response sometimes is excessive and can lead to tissue damage, organ failure and death, a process called sepsis. To end sepsis, bacterial growth has to stop. Antibiotic treatment usually can control bacterial growth and prevent the deadly consequences of sepsis, but increasing number of bacteria is becoming resistant to antibiotics.

In this study, the researchers investigated the possibility of recruiting phages in the fight against antibiotic–resistant bacteria, reviving the original idea of Felix d’Herelle, proposed in 1926.

“The driving force behind this project was to find phages that would kill 12 strains of antibiotic–resistant bacteria that were isolated from patients,” said co–author Dr. Robert Ramig, professor of molecular virology and microbiology at Baylor. “As the virologist on the team, my first contribution was to go phage hunting.”

“I have a number of phages in my lab, but none of them killed the antibiotic–resistant E. coli we were working on – the sequence type 131 currently pandemic across the globe,” Ramig said.

Birds and dogs often carry the bacteria the researchers were interested in, and may be one environmental reservoir of these pathogens. They also carry phages specific for those bacteria. Ramig, Maresso and Sabrina Green, a graduate student in the Molecular Virology Program at Baylor, went phage hunting in local parks and bird refuges to collect avian and canine feces.

“We isolated a number of phages from animal feces,” said Ramig. “No single phage would kill all the 12 bacterial strains, but collectively two or three of those phages would be able to kill all of those bacteria in cultures in the lab.”

This good news allowed the researchers to move on to the next step – determining whether the phages also would be able to kill the antibiotic–resistant bacteria in an animal model of sepsis.

One of the animal models the researchers worked with mimics how cancer patients develop potentially life–threatening infections during their cancer treatment.

Working in Maresso’s lab, Green developed a mouse model in which healthy mice received antibiotic–resistant bacteria that colonize their intestinal tract. “These mice showed no sign of disease,” Maresso said.

“But when the mice received chemotherapy,” Green said, “the bacteria moved from their intestine to major organs – this led to a fatal sepsis–like infection.”

In this animal model in which the immune system cannot keep in check antibiotic–resistant bacteria, Green tested whether the phages were able to do so.

“When the phages are delivered into the animals, their efficacy in reducing the levels of bacteria and improving health is dramatic,” Maresso said. “But that is not what is truly remarkable,” he continued. “What is remarkable is that these ‘drugs’ were discovered, isolated, identified and tested in a matter of weeks, and for less money than most of us probably spend in a month on groceries.”