Enzyme structure of bacteria that causes tuberculosis

Results on its interaction with antibiotics may lead to the development of new forms of treatment for this disease.

Tuberculosis is a chronic infection usually caused by a bacterium called Mycobacterium tuberculosis. This bacterium infects cells of the immune system called alveolar macrophages, which are responsible for removing pollutants and microorganisms from the surface of the alveoli, where the exchange of gases occurs during respiration.
It is estimated that approximately two billion people worldwide are infected with M. tuberculosis without symptoms. However, the clinical manifestations of the disease may appear at any time in life, especially when the immune system is weakened, such as due to malnutrition or diseases such as cancer and AIDS.
Tuberculosis is considered a curable disease when the patient is diagnosed and treated promptly with antibiotics. Nevertheless, the chronicity of this infection makes it difficult to eradicate bacteria altogether. Generally, patients must take the medication for several months, making it harder for them to persist in the treatment and favoring the emergence of antibiotic-resistant bacteria. In recent years, the emergence of new bacteria, resistant to routine treatments, has been a worldwide concern and it is imperative to seek new therapeutic strategies against this disease.

>Read more on the Brazilian Synchrotron Light Laboratory (LNLS) 

Image: (extract, full image here) Elements of the secondary structure of L,D-transpeptidase-3 from Mycobacterium tuberculosis acylated by an acetyl fragment derived from faropenem. Beta sheets in red, α-helices in yellow and the loops are shown in green. The figure shows, at the amino terminus (N-ter), the bacterial domain similar to immunoglobulin (BIg) and in the carboxy terminus the catalytic domain (CD). B-loop is a unique structure of this enzyme when compared to the other M. tuberculosis L,D-transpeptidases. In blue is shown an acetyl fragment covalently attached to cysteine 246 at the active site of the enzyme. Figure taken with Pymol.

UBC scientists break down tuberculosis structure

Scientists from the University of British Columbia have taken a crucial step towards starving out tuberculosis, following research into how the infection grows in the body.

Tuberculosis, a bacterial infection which generally affects the lungs, is a global threat; worldwide, it kills more people than HIV and malaria combined. In Canada, there are around 1,600 new cases of tuberculosis reported every year, with about 20 per cent of those cases affecting First Nations peoples, according to the Government of Canada. Researchers using the Canadian Light Source have investigated how the bacteria grow in lungs in an effort to better understand how tuberculosis can be treated.

Lindsay Eltis, a UBC professor of Microbiology and Immunology and Canada Research Chair in Microbial Catabolism and Biocatalysis, has spent the last 25 years studying bacteria and determining how they grow on different compounds. In 2007, Eltis’ group discovered that tuberculosis bacteria grow on cholesterol and that this is important for causing disease.

“Many bacteria, like humans, grow using glucose, a type of sugar. They derive energy from it, converting it to water and carbon dioxide, and use it to make building blocks essential to life. The tuberculosis bacterium is a bit unusual in that it can grow on cholesterol, deriving energy and essential building blocks from it,” explains Eltis. “This ability to grow on cholesterol helps the bacterium establish infection in our lungs.”

>Read more on the Canadian Light Source website

Image: Crystal structure of the newly imaged carbon-ring cleaving enzyme from the tuberculosis bacterium, IpdABMtb.
Credit: Lindsay Eltis