While drugs are available to treat tuberculosis, like so many other bacterial infections the disease is becoming more and more resistant to the best medications currently on offer. Scientists at Canada’s University of Guelph have uncovered a promising new pathway in the development of novel drugs, describing what they call a newly-discovered “keyhole” that can be targeted to starve tuberculosis-causing bacteria of the sustenance they need to survive.
The research focuses on a common mechanism shared by Mycobacterium tuberculosis and its relatives, which tap into our body’s cholesterol to breakdown steroids as a source of food. While these cousins of the M.tuberculosis don’t cause disease themselves, the fact that they use this same technique to fuel their activities makes them a useful model of study.
The University of Guelph team used the Canadian Light Source synchrotron to image these bacteria, which enabled them to identify the structure of an enzyme called acyl CoA dehydrogenase that is key to this steroid breakdown. This led them to create a picture of a “keyhole” that drugs would need to fit into to inactivate the enzyme, which they say provides a new target for the development of treatments for tuberculosis.
“We were surprised to observe that these enzymes are unusually adept at shifting their shapes as they go about their various tasks,” says Matthew Kimber, member of the research team. “This work helps us understand the exact shape of the keyhole a drug would need to fill to stop this enzyme in its tracks.”
We have seen some interesting advances of late in the pursuit of new treatments for tuberculosis that overcome the problem of drug-resistant bacteria, involving compounds found in scorpion venom and vitamin-based treatments. The scientists see starving the disease-causing bacteria as a particularly promising technique, and one that could even apply to treatment of other conditions such as inflammation and cancer.
“This should help in building a toolbox for making new steroid drugs, or making the ones we do use more efficiently,” says Kimber.
The research was published in the journal Biochemistry.
Source: Canadian Light Source
