Australia-U.S. team IDs way to curb tuberculosis bacterium growth

Two scientists in a lab

With the rise of multidrug-resistant tuberculosis and the variable efficacy of the BCG vaccine, the pressure is on to find new ways to combat the lung disease. Scientists from the University of Queensland and the University of California, San Francisco, have found a way to curb the growth of the bacterium that causes tuberculosis, highlighting a possible new route for treatments.

Cholesterol is known to affect Mycobacterium tuberculosis' virulence and ability to cause infection, the researchers said in a statement. So, the UCSF team, led by Paul Ortiz de Montellano, investigated the effect of compounds similar to cholesterol on the bacterium, both by feeding it the compounds and having it modify regular cholesterol in its cells. The Queensland team created inhibitors to act on the bacterium's enzymes that modified cholesterol.

They found that if the bacterium was given a modified version of cholesterol, it couldn't use it as an energy source and so, stopped growing, said James De Voss, professor of chemistry at the University of Queensland, in a statement. While this is a promising new take on inhibiting the bacterium's growth, De Voss said they "don't quite understand" how it works, but that the discovery "suggests a new way in which we can robustly inhibit growth of the TB bacterium." The findings are published in the Journal of Biological Chemistry.

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According to the World Health Organization, tuberculosis sickened approximately 9.6 million people and killed 1.5 million in 2014, with 95% of the cases occurring in developing countries. Of these patients, the agency estimated 480,000 developed multidrug-resistant TB, which occurs when the disease does not respond to the two most powerful antituberculosis drugs. Inappropriate or incorrect use of antimicrobial drugs, ineffective formulations and early termination of treatment can all contribute to drug resistance.

In September 2014, researchers at Brown University and MIT identified a class of antibiotics, ADEPs (cyclic acyldepsipeptides), that showed promise in fighting drug-resistant bacteria. While they were less effective killing M. tuberculosis cells, most likely because they are more complex than other bacteria, the team is working on new ADEP designs that will better attack the TB-causing bacterium.

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