The pathogen in question is Mycobacterium tuberculosis, which causes tuberculosis (TB). TB is one of the leading causes of death from infectious diseases worldwide, killing an estimated 1.6 million people in 2017.
M. tuberculosis produces a variety of chemicals that help it to survive and cause disease. One of these chemicals is mycolic acid, a waxy substance that forms the outer layer of the bacterium's cell wall. Mycolic acid is essential for the bacterium's survival, and it also helps it to resist antibiotics.
The researchers used a technique called X-ray crystallography to determine the structure of the enzyme that produces mycolic acid. This enzyme is called mycocerosic acid synthase (MAS).
The structure of MAS revealed that the enzyme has a tunnel-like shape. The tunnel is lined with amino acids that interact with the chemicals used to make mycolic acid. This interaction helps to guide the chemicals into the correct position for the reaction to take place.
The researchers also discovered that MAS is regulated by a small molecule called cyclic di-GMP. Cyclic di-GMP is produced by the bacterium in response to environmental signals, such as the presence of antibiotics. When cyclic di-GMP binds to MAS, it inhibits the enzyme's activity. This inhibition prevents the bacterium from making mycolic acid, which makes it more susceptible to antibiotics.
The discovery of the structure of MAS and its regulation by cyclic di-GMP could lead to new treatments for TB and other diseases caused by M. tuberculosis. By targeting MAS, researchers may be able to develop drugs that inhibit the enzyme's activity and make the bacteria more susceptible to antibiotics.
"Our findings provide a new understanding of how M. tuberculosis produces mycolic acid," said the study's lead author, Professor Jayna Bausch. "This information could lead to the development of new drugs that are more effective in treating TB and other diseases caused by this pathogen."
