Use biofilm’s own enzymes to defeat its ‘armor’

Researchers have developed a way to use the same enzymes that help microbes create biofilms to keep biofilms from forming and even destroy them.

Biofilms are slimy, glue-like membranes that microbes, like bacteria and fungi, make in order to colonize surfaces. They can grow on animal and plant tissues, and even inside the human body on medical devices such as catheters, heart valves, or artificial hips.

“Over 70 percent of hospital-acquired infections are actually associated with biofilms and we simply lack tools to treat them!”

Biofilms protect microbes from the body’s immune system and increase their resistance to antibiotics. They represent one of the biggest threats to patients in hospital settings.

The team’s research, which appears in the Proceedings of the National Academy of Sciences, creates a promising avenue for the development of innovative strategies to treat a wide variety of diseases and hospital-acquired infections like pneumonia, as well as bloodstream and urinary tract infection.

Biofilm-associated infections are responsible for thousands of deaths across North America every year. They are hard to eradicate because they secrete a matrix made of sugar molecules which form a kind of armor that acts as a physical and chemical barrier, preventing antibiotics from reaching their target sites within microbes.

“We were able to use the microbe’s own tools against them to attack and destroy the sugar molecules that hold the biofilm together,” says the study’s co-principal investigator, Don Sheppard, director of the Division of Infectious Diseases at the McGill University Health Center and scientist from the Infectious Diseases and Immunity in Global Health Program.

“Rather than trying to develop new individual ‘bullets’ that target single microbes we are attacking the biofilm that protects those microbes by literally tearing down the walls to expose the microbes living behind them. It’s a completely new and novel strategy to tackle this issue,” Sheppard says.

This work is the result of a four-year successful collaboration between Sheppard’s team and scientists in the laboratory of P. Lynne Howell, senior scientist in the Molecular Medicine program at the Hospital for Sick Children (SickKids). They have been working to combat biofilms for several years, focusing on two of the most common organisms responsible for lung infections: a bacterium called Pseudomonas aeruginosa and a fungus called Aspergillus fumigatus.

Biofilm bacteria linger on toys, books, cribs

Infections with these organisms in patients with chronic lung diseases like cystic fibrosis represent an enormous challenge in medical therapy.

While studying machinery that these organisms use to make their biofilms, the scientists discovered enzymes that cut up the sugar molecules, which glue biofilms together.

“Microbes use these enzymes to move sugar molecules around and cut them into pieces in order to build and remodel the biofilm matrix,” says Sheppard, who is also a professor in the medicine, microbiology, and immunology departments at the university. The researchers found a way to use these enzymes to degrade the sugar armor, exposing the microbe to antibiotics and host defenses.

“We made these enzymes into a biofilm destroying machine that we can use outside the microbe where the sugar molecules are found,” explains co-first study author Brendan Snarr, a doctoral student in Sheppard’s laboratory. “These enzymes chew away all of the sugar molecules in their path and don’t stop until the matrix is destroyed.”

“Previous attempts to deal with biofilms have had only limited success, mostly in preventing biofilm formation. These enzymes are the first strategy that has ever been effective in eradicating mature biofilms, and that work in mouse models of infection,” adds Sheppard.

“When we took the enzymes from bacteria and applied them to the fungi, we found that they worked in the same way on the fungi biofilm; which was surprising,” says Howell, the study’s co-principal investigator, who is also a professor in the biochemistry department at the University of Toronto.

“What’s key is that this approach could be a universal way of being able to leverage the microbes’ own systems for degrading biofilms. This has bigger implications across many microbes, diseases, and infections.”

“Over 70 percent of hospital-acquired infections are actually associated with biofilms and we simply lack tools to treat them!” says Sheppard. According to both lead scientists, the potential of this therapy is enormous and they hope to commercialize it in the coming years.

Drug fights biofilm and virus at the same time

The Canadian Institutes of Health Research (CIHR); Cystic Fibrosis Canada; the Natural Sciences and Engineering Research Council of Canada (NSERC); Canada Research Chairs Program; the Fonds de recherche Quebec santé (FRQS); SickKids Foundation; and the Canadian Glycomics Network (GlycoNet), part of the Networks of Centres of Excellence of Canada funded the study.

Source: McGill University