Odd structure in TB bacteria -a new drug target?
potential drug target in the cell walls of Mycobacterium
tuberculosis, the bacterium that causes TB, a disease that is
reappearing as new, multiresistant drug-strains.
The discovery could potentially be the starting point for investigations of its role in TB infection. As the sugar is unusual, enzymes that are necessary for its biosynthesis could be a viable point of attack for new tuberculosis medications.
The main component of the cell walls is a branched segment molecule made of sugar building blocks. The sugars involved are arabinose and mannose. Researchers discovered that mannose carried another type of sugar building block. This type of sugar consists of five carbon atoms (pento) and a sulphur atom (thio). This discovery is unusual because this is the first time that a sugar of this structure has been identified as a component of a polysaccharide.
The researchers from the University of Leeds took on the task of synthesizing all of the eight structural variations of this sugar. NMR spectroscopic comparison of the eight sugars with the "original" natural form then allowed the team to identify the correct structure, a "xylo" configuration. This is unusual, since sugars with the xylo configuration are found normally in plants, not in bacteria.
Dr Achim Treumann, lead author of this study told DrugResearcher.com: "In order to produce drugs that exploit this new discovery two main questions need to be answered. Is methyl-thio-xylofuranose (MTX) essential for the survival of the mycobacteria or for their infectivity? The answer could determine whether drugs directed against it would be useful."
"How do mycobacteria make this sugar? If its biosynthesis and the enzymes that take part in it are known (neither is), one can start designing inhibitors to these enzymes and observe their effects on mycobacteria."
Today, more than one-third of the world's population is infected with TB and more than two million people die each. Currently, more than 79 per cent of cases are identified as 'super strains,' resistant to three of the four current treatments. Drug resistant TB is responsible for more than 300,000 new cases per year occurring mainly in Eastern Europe and Central Asia.
The present treatment for TB involves a complex 10-month course of four different antibiotics. However, bacterial resistance has increased because many patients, particularly in developing countries, do not receive the correct medications for the full course of treatment.
