Scientists uncover a new one-two punch combination that knocks out infection.

Researhers find a new role oxidants play in fighting bacteria.

Toronto - For many years, we have heard about the harmful effects of oxidants (compounds that are highly reactive). They have been labelled as "bad" molecules because they are often associated with radiation exposure and the damage of cellular parts such as DNA and proteins. But not all oxidants are "bad".

Scientists at The Hospital for Sick Children (SickKids) have found that oxidants play a bigger role in regulating the immune system then was previously thought. The study, led by Dr. John Brumell, SickKids Senior Scientist and Associate Professor in the Department of Molecular Genetics  and Institute of Medical Science at The University of Toronto, is published in the March 30 advance online edition of the Proceedings of the National Academy of Sciences (USA).

The researchers studied autophagy, a normal process in which a cell destroys proteins and other substances within its own cellular architecture. Autophagy derives its name from Greek, literally meaning "self-eating". It involves the formation of autophagosomes, a membrane compartment inside the cell that engulfs unwanted material such as damaged cell parts or invading microbes. Autophagy has already been identified as an important defense mechanism against infections from bacteria, viruses and parasites. But how autophagy is regulated  has not been well understook.

In this study, scientists found autophagy of bacteria is regulated by oxidants. Normally our cells use a variety of antioxidant molecules and enzymes to protect themselves  from damage caused by oxidants. However when faced with infection, our cells utilize specific enzymes, the NOX-family enzymes, to generate that oxidants not only kill invading microbes on their own, but also trigger the activation of autophagy.

"This is an important finding since it shows that two very important system for killing bacteria in our cells connected," say Brumell. "The NOX-family enzymes generate oxidants to kill mirobes directly and the create also regulate autophagy.

The NOX-family enzymes are found in most cells of the human body. This study suggests that NOX family enzymes play a broad role in regulating autophagy under many physiological conditions, not just during infection. The understanding of how autophagy under many physiological conditions, not just during infection. The understanding of how autophagy is regulated will likely have significant medical relevance given that the process has been linked to many human disease, including cancer, neurodegenerative disease and inflammatory bowel disease.

The study was supported by the Burroughs Wellcome Fund, the Canada Foundation for Innovation, Ontario Innovation Trust SickKids Foundation, The Canadian Association of Gastroenterology, the Canadian Institute of Health Research, the Crohn's and Colitis Foundation of Canada and the McLaughlin  Centre for Molecular Medicine.

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For more information please contact:
Matet Nebres, matet.nebres@sickkids.ca
Suzanne Gold, suzanne.gold@sickkids.ca