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!
Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
09.12.2016 | Cold Spring Harbor Laboratory
Plant-based substance boosts eyelash growth
09.12.2016 | Fraunhofer-Institut für Angewandte Polymerforschung IAP
Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.
Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...
In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.
Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
09.12.2016 | Life Sciences
09.12.2016 | Ecology, The Environment and Conservation
09.12.2016 | Health and Medicine