New therapies for treating tuberculosis (TB) may stem from a novel discovery of a bacterial “dimmer switch” that might be helping the bug to evade the body’s defenses.

TB, caused by infection with Mycobacterium tuberculosis, kills about 1.5 million people worldwide and affects around 10 million individuals each year, according to the World Health Organization.  

Led by researchers at from The Hospital for Sick Children (SickKids) and University of Guelph, the discovery is described in a new paper in the Proceedings of the National Academy of Sciences, with first authors Yingke Liang, a PhD candidate in the Rubinstein Lab at SickKids, and PhD candidate Alicia Plourde at the University of Guelph.

“Our research group at SickKids has been using advanced microscopy methods to visualize the machines that power mycobacteria,” says Dr. John Rubinstein, a Senior Scientist in the Molecular Medicine program. “This work has relied on a large international network of collaborators, including Dr. Siavash Vahidi, an expert in the technique of mass spectrometry at University of Guelph.”

Research into bacteria complex uncovers potential drug target 

Energy production is carried out by several “respiratory Complexes”. In their new study, the researchers were able to determine the first structure of mycobacterial respiratory Complex I revealing how Complex I in mycobacteria differs from other living cells. One difference the researchers discovered is a “dimmer switch” within this complex that enables the bug to survive in many different environments.

Comparing respiratory Complex 1 to a car engine, the team found a new “engine part” that had gone unnoticed until now.

That extra part may help the bug hibernate in harsh, nutrient-scarce environments within the body by turning down energy production to the bare minimum for survival.  

“Several of the most recent new drugs and drug candidates for treating TB target mycobacterial energy production, but this process in mycobacteria is extremely complicated and not well understood,” says Rubinstein. “By visualizing these systems we can determine how mycobacterial energy production occurs and help guide the development of new TB therapies.”

Having found the protein dimmer switch, the researchers tested its function by removing it from bacteria. That prevented part of the bug’s respiratory system from assembling and working properly. 

The new finding opens the way to potential new drug treatments. “The research could help support the development of a therapy to inhibit the newly found part – or drugs to disable sensors that normally help the bug to sense its environment and trigger the dimmer switch,” said Vahidi, a professor in the Department of Molecular and Cellular Biology within the College of Biological Science at the University of Guelph.

Read the original release on the University of Guelph website.

This study was supported by the Canadian Institutes of Health Research (CIHR).