In search of new strategies against life-threatening tuberculosis infections, a team from the Technical University of Munich (TUM), as well as Harvard University and Texas A&M University in the USA have found a new ally. They discovered a substance that interferes with the mycomembrane formation of the bacterium. It 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. A team of scientists headed by Stephan A. Sieber, Professor of Organic Chemistry at TU Munich, 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 hypothesizes that similarly structured beta lactones could “mask” themselves as mycolic acid to enter the mycolic acid metabolic pathways and then block the decisive enzymes.
In the context of an extensive search, the interdisciplinary team of scientists hit the bullseye with the beta lactone EZ120. It does indeed inhibit the biosynthesis of the mycomembrane and kills mycobacteria effectively. Using enzyme assays and mass spectroscopy investigations, Dr. Johannes Lehmann, a researcher at the Chair of Organic Chemistry II at TU Munich, demonstrated during his doctoral work that the new inhibitor blocks especially the enzymes Pks13 and Ag85, which play a key role in the development of mycomembranes.
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,” says Prof. Sieber, who heads the Chair of Organic Chemistry II. “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.
Learn more: Double strike against tuberculosis
The Latest on: Tuberculosis
- FDA Approves New Drug to Help Fight Treatment-Resistant Tuberculosison August 16, 2019 at 8:02 am
The U.S. Food and Drug Administration has approved a new drug to help fight deadly types of tuberculosis that are highly resistant to treatment. The FDA announced Wednesday that the newly-approved ...
- Scientists Discover New Cure for the Deadliest Strain of Tuberculosison August 16, 2019 at 7:38 am
TSAKANE, South Africa — When she joined a trial of new tuberculosis drugs, the dying young woman weighed just 57 pounds. Stricken with a deadly strain of the disease, she was mortally terrified. Local ...
- A New Dose of Hope in the Battle With Tuberculosison August 16, 2019 at 7:36 am
Tuberculosis is the world’s deadliest infectious disease: Between 2007 and 2017, an estimated 94.5 million people caught tuberculosis, and more than 14 million died from it. Rising numbers are being ...
- Treatment for Extreme Drug-Resistant Tuberculosis Wins U.S. Government Approvalon August 16, 2019 at 6:49 am
The U.S. Food and Drug Administration has approved a drug regimen to treat an extreme form of multi-drug-resistant tuberculosis (TB). Nearly 90% of people infected with extensively drug-resistant (XDR ...
- How a new antibiotic destroys extremely drug-resistant tuberculosison August 16, 2019 at 6:25 am
The Food and Drug Administration on Wednesday approved a new antibiotic that, when combined with two existing antibiotics, can tackle the most formidable and deadly forms of tuberculosis.
- A new FDA-approved drug takes aim at a deadly form of tuberculosison August 16, 2019 at 3:24 am
An especially dangerous type of tuberculosis may have met its match. The U.S. Food and Drug Administration announced August 14 that it has approved the antibiotic pretomanid to help tackle what’s ...
- New treatment approved for drug-resistant tuberculosison August 15, 2019 at 11:18 am
(CNN)The US Food and Drug Administration approved a new treatment for highly drug-resistant tuberculosis, offering new hope in the fight against the world's most deadly infectious disease. TB most ...
- FDA approves drug for most deadly form of tuberculosison August 15, 2019 at 10:03 am
(HealthDay)—A new drug has been approved as part of a powerful, three-pronged treatment regimen for the most deadly strain of tuberculosis, the U.S. Food and Drug Administration announced Wednesday.
- FDA approves tuberculosis drug that works on hard-to-treat caseson August 14, 2019 at 2:00 pm
U.S. regulators have approved a new tuberculosis medication that shortens and improves treatment for the hardest-to-treat cases — a worsening problem in many poor countries. Decades of incomplete or ...
- After 20 years of research, RTI drug approved for drug-resistant tuberculosison August 14, 2019 at 12:53 pm
A new drug developed by RTI International scientists has been granted U.S. Food and Drug Administration (FDA) approval – offering hope to patients with drug resistant tuberculosis. The FDA's approval ...
via Google News and Bing News