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
- Mizzou Student Diagnosed With Active Tuberculosis on February 19, 2019 at 1:31 am
Feb. 19--COLUMBIA, Mo. (KFSM) — University of Missouri officials announced Monday (Feb. 18) that a student has been diagnosed with active tuberculosis (TB). According to the school’s Twitter account, ... […]
- Missouri student on Columbia campus has active tuberculosis on February 18, 2019 at 9:02 pm
COLUMBIA, Mo. (AP) — University of Missouri officials say a student on the Columbia campus has active tuberculosis and may have infected other people. The school announced Monday that the Boone County ... […]
- Student diagnosed with active tuberculosis at University of Missouri on February 18, 2019 at 7:28 pm
Feb. 18--COLUMBIA, Mo. — University of Missouri officials announced Monday that a student has been diagnosed with active tuberculosis. Load Error The university said the student has voluntarily left t... […]
- Mizzou student has active tuberculosis, school officials say on February 18, 2019 at 12:16 pm
A student at the University of Missouri in Columbia has active tuberculosis and possibly infected others, school officials announced Monday. School officials are investigating the case with the Boone ... […]
- University of Missouri student leaves campus after being diagnosed with tuberculosis on February 18, 2019 at 11:36 am
COLUMBIA, Mo. (KMOV.com) -- A student at the University of Missouri has left campus after reportedly contracting tuberculosis. The university announced the news on Twitter, saying the student left vol... […]
- Tuberculosis: Commandeering a Bacterial 'Suicide' Mechanism on February 18, 2019 at 11:13 am
The bacteria responsible for tuberculosis can be killed by a toxin they produce unless it is neutralized by an antidote protein. The European team of scientists behind this discovery is coordinated by ... […]
- Suicide system in tuberculosis bacteria might hold key to treatment on February 18, 2019 at 9:00 am
This is the high-resolution structure of the toxin-antitoxin system. Credit: EMBL Hamburg Tuberculosis (TB) is one of the top ten causes of death worldwide. In 2017, 10 million people around the ... […]
- Tuberculosis diagnosis sends U Missouri student packing on February 18, 2019 at 7:30 am
A student has voluntarily left the campus of the University of Missouri after being diagnosed with active tuberculosis, the school announced. School and health officials were working closely to identi... […]
- To end tuberculosis, we must invest in a more streamlined approach on February 18, 2019 at 6:30 am
The views expressed by contributors are their own and not the view of The Hill When I was a young doctor in Turkey, I quickly learned to take a bird’s eye view of health care. I started working ... […]
via Google News and Bing News