Have you ever heard of biofilms? They are slimy, glue-like membranes that are produced by microbes, like bacteria and fungi, 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. Biofilms protect microbes from the body鈥檚 immune system and increase their resistance to antibiotics. They represent one of the biggest threats to patients in hospital settings. But there is good news 鈥� a research team led by the Research Institute of the 91社区 Health Centre听(RI-MUHC) and The Hospital for Sick Children (SickKids) has developed a novel enzyme technology that prevents the formation of biofilms and can also break them down.
This finding, recently published in听Proceedings of the National Academy of Sciences (PNAS),听creates a promising avenue for the development of innovative strategies to treat a wide variety of diseases and hospital-acquired infections like pneumonia, bloodstream and urinary tract infection.听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 armour that acts as a physical and chemical barrier, preventing antibiotics from reaching their target sites within microbes.
鈥淲e were able to use the microbe鈥檚 own tools against them to attack and destroy the sugar molecules that hold the biofilm together,鈥� says the study鈥檚 co-principal investigator, Dr. Don Sheppard, director of the Division of Infectious Diseases at the MUHC and scientist from the Infectious Diseases and Immunity in Global Health Program at the RI-MUHC. 鈥淩ather than trying to develop new individual 鈥榖ullets鈥� 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鈥檚 a completely new and novel strategy to tackle this issue.鈥�
This work is the result of a four-year successful collaboration between Dr. Sheppard鈥檚 team and scientists in the laboratory of Dr. P. Lynne Howell, senior scientist in the Molecular Medicine program at 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听Pseudomonas aeruginosa听and a fungus called听Aspergillus fumigatus. 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. 鈥淢icrobes use these enzymes to move sugar molecules around and cut them into pieces in order to build and remodel the biofilm matrix,鈥� says Dr. Sheppard, who is also a professor in the departments of Medicine and Microbiology and Immunology at 91社区. The researchers found a way to use these enzymes to degrade the sugar armour, exposing the microbe to antibiotics and host defenses.听
鈥淲e made these enzymes into a biofilm destroying machine that we can use outside the microbe where the sugar molecules are found,鈥� explains co-first study author Brendan Snarr, a PhD student in Dr. Sheppard鈥檚 laboratory. 鈥淭hese enzymes chew away all of the sugar molecules in their path and don鈥檛 stop until the matrix is destroyed.鈥�
鈥淧revious 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,鈥� adds Dr. Sheppard.
听鈥淲hen 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,鈥� says the study鈥檚 co-principal investigator, Dr. P. Lynne Howell, who is also a professor in the Department of Biochemistry at the University of Toronto. 鈥淲hat鈥檚 key is that this approach could be a universal way of being able to leverage the microbes鈥� own systems for degrading biofilms. This has bigger implications across many microbes, diseases and infections.鈥�
鈥淥ver 70 percent of hospital-acquired infections are actually associated with biofilms and we simply lack tools to treat them!鈥� states Dr. Sheppard. According to both lead scientists, the potential of this novel therapy is enormous and they hope to commercialize it in the coming years.
About the study
This study was funded by the Canadian Institutes of Health Research (CIHR), Cystic Fibrosis Canada, the Natural Sciences and Engineering Research Council of Canada, Canada Research Chairs Program, the Fonds de recherche Quebec sant茅 (FRQS) and SickKids Foundation.听
Dr. Howell and Dr. Sheppard are also Network Investigators with the Canadian Glycomics Network (), part of the Networks of Centres of Excellence of Canada that has provided financial support for this work.
For additional information, we invite you to read the study.听顿翱滨:听
About the Research Institute of the MUHC
The Research Institute of the 91社区 Health Centre (RI-MUHC) is a world-renowned biomedical and healthcare research centre. The Institute, which is affiliated with the Faculty of Medicine of 91社区, is the research arm of the 91社区 Health Centre (MUHC) 鈥� an academic health centre located in Montreal, Canada, that has a mandate to focus on complex care within its community. The RI-MUHC supports over 460 researchers and close to 1,300 research trainees devoted to a broad spectrum of fundamental, clinical and health outcomes research at the Glen and the Montreal General Hospital sites of the MUHC. Its research facilities offer a dynamic multidisciplinary environment that fosters collaboration and leverages discovery aimed at improving the health of individual patients across their lifespan. The RI-MUHC is supported in part by the Fonds de recherche du Qu茅bec 鈥� Sant茅 (FRQS).听
About The Hospital for Sick Children
The Hospital for Sick Children (SickKids) is recognized as one of the world鈥檚 foremost paediatric health-care institutions and is Canada鈥檚 leading centre dedicated to advancing children鈥檚 health through the integration of patient care, research and education. Founded in 1875 and affiliated with the University of Toronto, SickKids is one of Canada鈥檚 most research-intensive hospitals and has generated discoveries that have helped children globally.听 Its mission is to provide the best in complex and specialized child and family-centred care; pioneer scientific and clinical advancements; share expertise; foster an academic environment that nurtures health-care professionals; and champion an accessible, comprehensive and sustainable child health system. SickKids is proud of its vision for Healthier Children. A Better World. For more information, please visit . Follow us on Twitter (@SickKidsNews) and Instagram (@SickKidsToronto)
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Julie Robert
Communications Coordinator 鈥� Research, 91社区 Health Centre
julie.robert [at] muhc.mcgill.ca听
514 934-1934 ext. 71381听
Suzanne Gold
Senior Communications Specialist- Media Relations, SickKids
suzanne.gold [at] sickkids.ca
416 813-7654 ext. 202059
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