Multi drug-resistant strains of Mycobacterium tuberculosis, the bacterium that causes TB, sparked concern but the recent emergence of extensively drug-resistant strains (XDR-TB) means the search for new treatments is imperative.
Unlike human cells, bacteria have cell walls. Molecules called mycolic acids form a vital part of these walls. To produce them, bacteria carry out several processes but until recently, scientists were unsure of the genes that control each step. One vital step is dehydration - the removal of a water molecule to lengthen the acid chain. Researchers from the University of Birmingham have shown that the gene Rv0636 controls this step, which provides new avenues for the development of treatments for TB.
"FAS-II is a group of enzymes that work together to carry out dehydration," said Professor Gurdyal Besra from the University of Birmingham. "We know that the molecules NAS-21 and NAS-91 can stop these enzymes from building cell walls, so we looked at their effect on Mycobacteria. We also wanted to find out if one of the enzymes is coded for by the gene Rv0636."
Professor Besra and his colleagues made modifications to NAS-21 and NAS-91, making several analogues based on the original molecules. They then tested these analogues to see if they stopped the enzymes from working. "Both series of compounds demonstrated activity against the FAS-II enzymes alone," said Professor Besra. "When we tested them against live bacterial cells we noticed that some of the analogues stopped the cells from building mycolic acids, which effectively killed them.
"We also tested them on bacteria that were overexpressing Rv0636, which meant they were producing extra enzymes. These cells were resistant to NAS-21 and NAS-91, suggesting that the gene Rv0636 does code for an enzyme in the FAS-II complex," said Professor Besra. "So we have solved the mystery.
The researchers have also identified a new class of compounds that could be developed into successful treatments for tuberculosis that are urgently required in the future. "The emergence of drug-resistant strains of Mycobacterium tuberculosis has highlighted the need for new TB drugs. We hope our discovery will lead to a new rationale for the design of treatments," said Professor Besra.
Lucy Goodchild | EurekAlert!
Link Discovered between Immune System, Brain Structure and Memory
26.04.2017 | Universität Basel
Researchers develop eco-friendly, 4-in-1 catalyst
25.04.2017 | Brown University
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
26.04.2017 | Materials Sciences
26.04.2017 | Agricultural and Forestry Science
26.04.2017 | Physics and Astronomy