New drugs to prevent tuberculosis could be developed thanks to this novel cell wall breakthrough

Research has identified a novel regulatory mechanism, which when deactivated, results in the death of the life-threatening pathogen.

New drugs to prevent tuberculosis could be developed thanks to novel research conducted by a team from our Department of Infection, Immunity and Inflammation.

According to the World Health Organization, tuberculosis claimed over 1.3 million lives in 2016. The causative agent of tuberculosis, Mycobacterium tuberculosis, is a highly successful pathogen which can survive and grow in humans for decades. 

M. tuberculosis is a slow growing bacterium with a very thick and complex cell wall that is resistant to many common antibiotics, requiring the development of new drugs and approaches in order to stop the deadly disease. 

Dr Galina Mukamolova, who led the study published in the journal Cell Reports, said: “M. tuberculosis is a nasty pathogen which is very difficult to treat because of its unique biology. However, our research revealed weakness and vulnerable sides of this pathogen. We have shown that inactivation of just one protein can result in dramatic consequences. We can interfere into the very sophisticated mechanism for regulation of cell wall biosynthesis described in our study in order to kill M. tuberculosis.”

The Leicester team examined a protein called protein kinase B (PknB) found in M. tuberculosis and found the reasons why it is necessary for growth in the pathogen.

PknB has been known for many years and extensively studied by many scientific groups. Previously, scientists showed that it was somehow involved in regulation of cell wall biosynthesis, however the precise mechanism was not clear. 

“We have shown that CwlM, another protein required for M. tuberculosis growth, is the main protein which is phosphorylated by PknB,” explains Dr Mukamolova. “This function makes PknB indispensable for the growth of M. tuberculosis. We found that two forms of CwlM (phosphorylated and non-phosphorylated) coexist in growing bacteria in different cellular compartments and may regulate different arms of the same process.

“Our research suggests that inactivation of CwlM, for example by using novel drugs, would result in death and lysis of M. tuberculosis. This is an excellent target for new drug development, which is particularly important because of tuberculosis’ rising resistance to existing drugs.”