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Industry Partnerships and Commercialization

Featured Technologies

Multi-platform technology for microbial biofilm breakdown

By Jacob Sintzel, Strategic Communications Intern 

According to the World Health Organization, antibiotic resistance in pathogens is one of the most pressing public health emergencies today. As a growing number of bacteria, fungi and infections grow resistant to existing antibiotic treatments, the more it threatens the state of our global health, food security and economy.

One of the most exciting solutions on the horizon to combat antibiotic resistance is currently in development here at the SickKids Research Institute.

 A team of SickKids researchers, Drs. Lynne Howell and Perrin Baker, in collaboration with McGill University researcher Dr. Don Sheppard are focusing on eliminating biofilm walls, a protective barrier created by bacterial and fungal colonies. According to Howell, a Senior Scientist in Molecular Medicine at SickKids and Professor in the Department of Biochemistry at the University of Toronto, a biofilm is a community of cells embedded in a self-produced structure called an extracellular polymeric matrix (EPM). The cellular community within the EPM can consist of just a single species or multiple types of bacteria. The actual polymeric substance surrounding the bacteria is built from a variety of substances such as proteins, DNA, sugars and lipids, all of which the bacteria secretes. 

“Think of it as a gooey mess into which your bacteria are embedded,” says Howell. These walls are linked to as many as 80 per cent of all human infections as they block out immune system responses and create a drug-tolerant environment that allows microbes to thrive."

“The biofilm you’re probably most familiar with is the scum that forms on your teeth,” says Baker, a Research Fellow in Molecular Medicine at SickKids. 

Similar to dental biofilms, Drs. Howell and Baker’s research endeavours at SickKids concentrate on biofilms formed in the lungs and in glutens. More specifically, the duo has dedicated significant attention towards a particular bacterial species found in cystic fibrosis patients called Pseudomonas aeruginosa. The biofilm wall produced by Pseudomonas makes it immune to the majority of available antibiotic treatments and often leads to lung failure in patients with this disorder. The standard course of treatment for these infections is through an antibiotic called tobramycin. However, since 1998, the bacteria’s resistance to tobramycin has risen by upwards of 20 per cent. Drs. Howell and Baker hope their new technology, currently undergoing preclinical trials on animal models, will prove successful in reversing this trend in the near future. Like other species of bacteria and fungi, Pseudomonas have specialized enzymes known as glycoside hydrolases, which help build its biofilm wall. Howell describes these enzymes operating as a machine, producing and exporting the sugar polymers that form the bulk of the bacteria’s outside shield.

While investigating further into the function of these specialized enzymes, they discovered that two of these glycoside hydrolases (PelAh and PslGh) are capable of directly targeting and degrading the wall’s sugar polymers. Baker likens this technology to the Trojan horse used to enter the mythological city of Troy. 

“It’s very difficult to penetrate a walled city, so our technology utilizes enzymes that act almost like scissors by cutting and breaking down the biofilm wall,” says Baker. 

Once the wall has been disrupted, the immune system and antibiotics are able to get in and work effectively to kill the bacteria. In addition, the team has proven that these enzymes do not harm human cells and help improve the body’s innate immune response to better fight off infections.

Both researchers envision this technology being used in a multitude of applications, whether that is treating wound infections or being used with existing antibiotic regimens to cure chronic diseases.

“In addition to the enzymes found in Pseudomonas biofilms, we have also found enzymes that work on fungal biofilms as well as those for both gram-positive and gram-negative bacteria,” says Howell.

This collection of enzymes acts, in essence, as a toolkit by providing treatments for specific pathogenic bacteria in ways that traditional antibiotics cannot. Antibiotics will generally kill multiple types of bacteria, sometimes those that are important for maintaining our health and wellbeing, Baker explains. As a consequence of eliminating the good bacteria, you may leave yourself more susceptible to other infections.

 “The nice thing about our technology is that they have this exquisite specificity in most cases to clear out pathogenic bacteria but not the bacteria in our bodies that we require to survive,” says Baker. 

Industry Partnerships & Commercialization (IP&C) at SickKids has played an integral role in the progress of this technology. The team works to support SickKids staff throughout the commercialization process in order to turn ideas into marketable matter. While Baker says that he would love to see all of the discoveries in the lab be used to improve health outcomes, he understands that securing intellectual property rights is vital. 

“If we simply just publish our work, a drug company, for example, who probably has the best ability to push this technology won’t be able to generate any money and handle the necessary costs associated with clinical trials,” says Baker. 

In addition to helping protect the research team’s intellectual property through a provisional patent, IP&C has assisted in raising development funds and connecting Howell and Baker with industry and venture capital. 

“The IP&C team have helped us with where we should be targeting our technology by getting us to talk to venture capitalists and other people that could potentially provide funding in the future,” says Howell.

The next step in determining the success of this technology will be to test the efficacy of the enzymes on animal models. 

“We have compiled a load of data from the lab and now we have to show that when you actually treat an infection in an animal, that it works,” says Howell.

This promising technology has the potential to impact antibiotic resistance on a global scale. Learn more about the team’s latest research on pathogenic microorganism.