Washington: Tuberculosis is an infectious disease that usually affects the lungs. Compared with other diseases caused by a single infectious agent, tuberculosis is the second biggest killer, globally.
And now in search of new strategies against life-threatening tuberculosis infections, a group of researchers have found a new ally. The team has discovered a substance that interferes with the mycomembrane formation of the bacterium.
The substance is effective even in low concentrations and when combined with known antibiotics their effectiveness is improved by up to 100-fold. Among the greatest challenges when treating life-threatening tuberculosis infections is the increasing resistance to antibiotics. But the pathogen itself also makes the life of doctors difficult - its dense mycomembrane hampers the effect of many medications.
The scientists have discovered a substance that unsettles the formation of this membrane significantly. The team hypothesises 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 has hit the bulls-eye with the beta lactone EZ120 and found that it does indeed inhibit 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. The scientists suspect that disrupting the mycomembrane enables antibiotics to enter the bacteria more easily. This is a new mode of action and might be a starting point for novel tuberculosis therapies," said study's lead author Stephan A. Sieber.
The study published in journal Angewandte Chemie International Edition.
