Quirks & Quarks

Bacteria-hunting viruses can track down antibiotic-resistant bugs where they hide

Bacteriophages could potentially help us mitigate the rising threat of antibiotic resistance.

Bacteriophages could potentially help us mitigate the rising threat of antibiotic resistance

Colonies of E. coli bacteria grown in a petri dish. U.S. health officials on May 26, 2016 reported the first case in the country of a patient with E. coli bacteria carrying the mcr-1 gene, an infection resistant to all known antibiotics. (file) (CDC / REUTERS)

A team of researchers in the U.S. has identified a way to fight antibiotic-resistant bacteria that take refuge in remote parts of the human gut. These bacteria are particularly problematic because they don't create illness where they hide, but invade other parts of the body from their intestinal refuge, causing a range of troublesome infections.

To fight these bacteria, the scientists found a bacteria-fighting virus — known as a bacteriophage, or "phage" for short — by screening for it in human sewage. The phage has unique properties that allow it to break into the difficult-to-access refuge where the bacteria hide in our intestines.

"There are E. coli [bacteria] that live inside of us and are kind of ticking time bombs waiting for our immune system to be compromised, to infect and eventually get into our blood system," said Sabrina Green, the director of research and development for Tailor Labs at Baylor College of Medicine in Texas.

These particular strains of E. coli live in our gut where, ordinarily, they don't cause us any problems, but can become deadly when they exit the intestine and cause infections in the urinary tract or bloodstream.

They're becoming ever more troublesome as they develop resistance to antibiotics, a major concern in medicine these days. The more we use antibiotics to treat these kinds of infections, the more these bacteria bacteria evolve to find ways around these drugs.

There are E. coli that live inside of us and are kind of ticking time bombs waiting for our immune system to be compromised, to infect and eventually get into our blood system.- Sabrina Green, PhD, Baylor College of Medicine at Tailor Labs

This is why scientists predict that without alternate strategies to fight bacteria, by 2050 our current antibiotics could be largely useless against multidrug-resistant bacteria. It's estimated this could result in 10 million deaths a year.

Green explained to Quirks & Quarks host Bob McDonald how the complex environment inside the human intestine, where the bacteria hide, makes it challenging for antibiotics to reach them in order to kill them. The bacteria have adapted to inhabit the mucous layer that coats and protects the cells that line our intestines. 

"[The bad bacteria] can hide deep within the mucous layer that protects us from most pathogens," she said.

This picture shows syringes containing diluted solutions of phages from three different concentrated types of phages prepared at the Croix-Rousse hospital, in Lyon, France. Phages are showing to be a possible alternative to antibiotics as a treatment against multidrug resistant bacteria. (file) (Romain Lafabregue / AFP via Getty Images)

Selecting the right phage for the job

Bacteria-eating phages — one of the most common and diverse organisms in the biosphere — can be found anywhere there are bacteria.

To find just the right phage to seek out and destroy bacteria living in the gut, Green and her colleagues turned to human sewage.

After filtering out what she describes as "all the bacteria and all the gunk," researchers incubate the remaining viruses, and then expose them to the antibiotic-resistant bacteria and gut-like conditions.

"This way, we are selecting for [a] phage that can not only kill that bacteria, but we create these gut culture systems that kind of mimic our gut, so that we can find [a] phage that can kill in this environment as well." 

When the research team tested the phage candidate they identified in mice that were infected with antibiotic resistant gut bacteria, it worked incredibly well, Green said.

"We found that this phage could completely eliminate this E. coli that was present."

Phage therapy is has been widely used in Eastern Europe, as seen in this 2005 photo taken at the Eliava Institute of Bacteriophage, Microbiology and Virology in Tbilissi, Georgia. (Vano Shlamov / AFP via Getty Images)

Phage can keep up with antibiotic resistance

One advantage of using phage therapy is that phage can evolve to keep up with bacteria.

"These antibiotics are fixed chemicals, but phage, however, are viruses and they can change and we can evolve them to overcome this bacterial resistance against it," Green added.

When she and her colleagues tested this phage on a patient with a urinary tract infection who came to the Tailor Service Center — where she prepares phage cocktails for patients with multidrug resistant infections — she said it worked "very well."

She and her colleagues tested this phage on a patient at the Tailor Service Center, where Green prepares phage cocktails for patients with multidrug-resistant infections. The scientist said the phage worked "very well" on the patient's urinary tract infection. 

These antibiotics are fixed chemicals, but phage, however, are viruses and they can change and we can evolve them to overcome this bacterial resistance against it.- Sabrina Green, PhD, Baylor College of Medicine at Tailor Labs

 

Interestingly, she said, while the phage completely cleared the infection in this patient, it didn't entirely clear resistant bacteria in the gut, but it did seem to push it to adapt into something less pathogenic.

"Sometimes, bacteria, they'll change to resist the phage, but those changes could be detrimental to the bacteria so that it's no longer as infectious or can no longer survive in that environment," she said.

Green said she hopes to further develop phage therapy options — still considered experimental in the U.S. and Canada — for specific infections, and get them into clinical trials. 

Produced and written by Sonya Buyting

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