Berlin: In search of new strategies against the life-threatening tuberculosis infection, scientists have discovered a substance that prevents the membrane formation of the bacterium. The substance is effective even in low concentrations and when combined with known antibiotics its effectiveness is improved by up to 100-fold, said researchers from the Technical University of Munich (TUM) in Germany and Harvard University in the US.
Among the greatest challenges when treating tuberculosis infections is the increasing resistance to antibiotics, the researchers said. However, the dense mycomembrane hampers the effect of many medications, according to the study published in the journal Angewandte Chemie. The team of scientists has discovered a substance that perturbs the formation of this membrane significantly.
The mycomembrane of the tuberculosis pathogen Mycobacterium tuberculosis consists of a lipid double layer that encapsulates the cell wall, forming an exterior barrier. Structural hallmarks are mycolic acids, branched beta- hydroxy fatty acids with two long hydrocarbon chains. The team hypothesised that similarly structured beta lactones could "mask" themselves as mycolic acid to enter the mycolic acid metabolic pathways and then block the decisive enzymes. The interdisciplinary team of scientists found that the beta lactone EZ120 inhibits the biosynthesis of the mycomembrane and kills mycobacteria effectively.
EZ120 is effective even in low doses, easily passes the mycomembrane and exhibits only low toxicity to human cells. The combined application of this substance with known antibiotics showed a synergistic effect leading to significantly increased effectiveness. "Vancomycin, a common antibiotic, and EZ120 work together very well. When used together, the dose can be reduced over 100-fold," said Stephan A Sieber from TUM.