New treatment option against tuberculosis

New therapeutic approach enables more efficient treatment of tuberculosis

Tuberculosis infections can quickly become life-threatening and in many cases the treatment is made more difficult by resistance of the pathogens. New therapeutic approaches are therefore needed that enable efficient treatment even with existing resistance. Here, scientists from the Technical University of Munich (TUM), Harvard University and Texas A & M University have now identified a drug that, in combination with antibiotics, leads to a significant improvement in therapy.

The researchers "found a substance that disturbs the structure of the cell membrane of the bacterium" and "already in low concentration and in combination with an already known antibiotic enhances the effect by a factor of 100," the TMU. In the treatment of life-threatening tuberculosis infections, the growing number of antibiotic resistances is one of the biggest challenges and also the therapy is hampered by the dense mycomembrane of the pathogens, as the membrane reduces the effect of many drugs.

A newly discovered substance could enable significant improvements in tuberculosis therapy in the future. (Image: Zerbor / fotolia.com)

Mykomembran protects the pathogens

"The mycomembrane is a lipid bilayer that wraps around the cell wall and forms an outer barrier," explain the experts. The research team led by Professor Stephan A. Sieber from the TUM has now identified a substance in his current study that sensitively disturbs the structure of this membrane of the tuberculosis pathogen Mycobacterium tuberculosis. For this they searched for a substance that has a similar structure to the mycolic acids, which form a major structural component of the mycemembrane. The researchers published their results in the journal "Angewandte Chemie".

Inhibited biosynthesis of mykomembrane

The mycolic acids are branched ß-hydroxy fatty acids with two long hydrocarbon chains and similar beta lactones could use the same metabolic pathway as these and block the crucial enzymes, the researchers hypothesized. This assumption has been confirmed in the investigations and the scientists discovered with beta-lactone "EZ120" a substance that actually inhibits the biosynthesis of mycemembrane and kills the mycobacteria effectively.

EZ120 is already effective in low dose

Using enzyme assays and mass spectrometry, Dr. Johannes Lehmann, a member of the Chair of Organic Chemistry II of the Technical University of Munich, show that the new inhibitor mainly blocks the enzymes Pks13 and Ag85, which play a crucial role in the development of mycemembranes, according to the TUM. In addition, EZ120 already works in a low dose, the mycomembrane can overcome well and shows only low toxicity to human cells, the University further reports.

Combined use with antibiotics

With combined use of antibiotics and EZ120, the scientists say the effectiveness of antibiotics is increased significantly. "Vancomycin, a common antibiotic, and EZ120 work well together," said Professor Sieber. Co-administration allows a reduction in the dose of antibiotics more than 100-fold. Presumably the antibiotics can penetrate through the weakening of the Mykomembran more easily into the bacteria, explain the expert. In the opinion of the researchers, this could be a starting point for novel tuberculosis therapies. (Fp)