The fungus Aspergillus fumigatus produces a sticky sugar molecule (seen in this microscopic image as a speckled meshwork) in order to make its biofilm. It covers the fungus and allows it to stick to surfaces and tissues, making it difficult to remove and treat patients. Scientists from the Research Institute of the MUHC and SickKids have developed a new innovative technique aimed at destroying biofilms.Technique used:  Scanning electron microscopy

The fungus Aspergillus fumigatus produces a sticky sugar molecule (seen in this microscopic image as a speckled meshwork) in order to make its biofilm. It covers the fungus and allows it to stick to surfaces and tissues, making it difficult to remove while also acting as a protective barrier against antibiotics and the immune system defences. Scientists from the Research Institute of the MUHC and SickKids Hospital have developed a new innovative technique aimed at destroying biofilms and making the microbe open to treatment. (Image technique used: Scanning electron microscopy
Photo Credit: Fabrice N. Gravelat, Research Institute of the McGill University Health Centre

Potentially huge breakthrough in treating infections

Canadian researchers have made what holds promise as an enormous advance in fighting infections.

Teams in Toronto (Sick Kids Hospital/U of T)  and Montreal combined their skills to develop a way to break through microbial defences, their “biofilm” which has long been a major hurdle in successful treatment of infections.

Dr. Don Sheppard is a co-leader of the research teams. He is director of the Division of Infectious Diseases at the MUHC and scientist from the Infectious Diseases and Immunity in Global Health Program at the Research Institute (RI-MUHC) and a professor in the departments of Medicine and Microbiology and Immunology at McGill University in Montreal.

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Canadian researchers developed a novel enzyme technology to fight biofilms From left to right: Brendan D. Snarr and Donald C. Sheppard from the Research Institute of the McGill University Health Centre (Montreal) and P. Lynne Howell, Natalie C. Bamford and Perrin Baker from The Hospital for Sick Children (Toronto).
Canadian researchers developed a novel enzyme technology to fight biofilms From left to right: Brendan D. Snarr and Donald C. Sheppard from the Research Institute of the McGill University Health Centre (Montreal) and P. Lynne Howell, Natalie C. Bamford and Perrin Baker from The Hospital for Sick Children (Toronto). © McGill University Health Centre

Microbial infections are a major and too often deadly occurance in hospitals. Bacteria and fungus create biofilms which are a slimy, glue-like membrane which enable them to colonize surfaces and stick fast.

This can be anything from plastic catheters, to artificial hip replacements, heart valves, or human tissues.

In addition, the biofilm the microbes secrete also acts as armour protecting them from physical or chemical attack and as such are barriers to the body’s own immune systems attacks, and to various antibiotics and anti-fungals, reducing their effectiveness.

Untreatable infections result in thousands of hospital deaths in North America every year.

Fungal biofilm formation The fungus Aspergillus fumigatus (in red) produces a sticky sugar molecule (in green) in order to make its biofilm. It covers the fungus and allows it to stick to surfaces and tissues, making it difficult to remove and treat patients. Scientists from the Research Institute of the MUHC and SickKids have developed a new innovative technique aimed at destroying biofilms. Technique used: confocal fluorescent microscopy
Fungal biofilm formation: The fungus Aspergillus fumigatus (in red) produces a sticky sugar molecule (in green) in order to make its biofilm. It covers the fungus and allows it to stick to surfaces and tissues and which acts as a protective armour against physical and chemical attack, making it difficult to remove and treat. Scientists from the Research Institute of the MUHC and SickKids have developed a new innovative technique aimed at destroying biofilms. Technique used: confocal fluorescent microscopy © Brendan Snarr, Research Institute of the McGill University Health Centre

Knowing the problem of trying to get drugs or even the body’s own immune system, to break through the biofilm to get at the microbial infection, research teams led by the Research Institute of the McGill University Health Centre  (RI-MUHC) and The Hospital for Sick Children (SickKids) took a unique research direction.

They sought to first understand how microbes build the biofilm protection, and then sought out weaknesses. The microbes secrete a matrix made of sugar molecules. The microbes also use enzymes which cut and reshape the biofilm enabling the infection to grow and multiply.

After four years of research, the Canadian teams were able to recreate the enzyme, removing the microbial “control”.

They have developed a novel enzyme technology that prevents the formation of biofilms and can also break them down.  When the “uncontrolled” enzyme encounters the sugar molecules of the biofilm it simply begins to chew away at them and doesn’t stop until they’re all gone.

Effect of the enzyme therapy on the fungal biofilm formation When the newly-discovered enzymes are added to the fungus Aspergillus fumigatus (in red), they degrade the sugar molecules making the biofilm (sugar molecules are hard to be detected by staining in green). Scientists have found this treatment also reduces the adherence of the fungus to surfaces or tissues, as well as its virulence.Technique used: confocal fluorescent microscopy
Effect of the new enzyme therapy on the fungal biofilm formation When the newly-discovered enzymes are added to the fungus Aspergillus fumigatus (in red), they degrade the sugar molecules making the biofilm (sugar molecules are hard to be detected by staining in green). Scientists have found this treatment also reduces the adherence of the fungus to surfaces or tissues, as well as its virulence. Technique used: confocal fluorescent microscopy © Brendan Snarr, Research Institute of the McGill University Health Centre

They sought to first understand how microbes build the biofilm protection, and then sought out weaknesses. The microbes secrete a matrix made of sugar molecules and enzymes which cut and reshape the biofilm as the infection grows.

After four years of research, the Canadian teams were able to recreate the enzyme, removing the microbial “control”.

They have developed a novel enzyme technology that prevents the formation of biofilms and can also break them down.  When the “uncontrolled” enzyme encounters the sugar molecules of the biofilm it simply begins to chew away at them and doesn’t stop until they’re all gone.

“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”, says Dr.Sheppard.

By creating their own enzyme, the biofilms are broken down enabling drugs to directly target the infection, greatly increasing their effectiveness.

VIDEO: Biofilms grow on the fungus Aspergillus fumigatus (in red) as seen in this 20 hour time-lapse video.
Credit: Brendan Snarr, Research Institute of the McGill University Health Centre

Dr. P. Lynne Howell, senior scientist in the Molecular Medicine program at Toronto’s SickKids Hospital is quoted in a news release saying, “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.”

In fact, after promising results against  a common bacteria (Pseudomonas aeruginosa), they applied the technology against a common fungus, (Aspergillus fumigatus) and found similar successful results.

The researchers note that the process of creating biofilms seems to be common to a wide variety of microbes and so this technology could be used in treatment in a vast number of human, animal, and even plant diseases.

This study was funded by 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) and SickKids Foundation.

Dr. Howell and Dr. Sheppard are also Network Investigators with the Canadian Glycomics Network (GlycoNet), part of the Networks of Centres of Excellence of Canada that has provided financial support for this work.

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