Tuberculosis, or TB, is a highly contagious disease of the lungs that was thought to have been virtually eliminated by the 1960s, but is now resurgent and kills nearly two million people worldwide every year. New infections are occurring at a rate of one per second.
Of equal concern is the dramatic rise in the incidence of new strains of TB that are resistant to traditional antibiotics. As a result, the World Health Organisation, the Bill Gates Foundation and the European Union have all launched initiatives to tackle the problem.
Now, biologists at The University of Manchester have shown that chemicals called azoles – the active agent in many antifungal drugs – kill the TB bacteria, and could be effective in tackling the emerging drug-resistant strains.
“TB is back with a vengeance with a third of the world’s population currently infected,” said Professor Andrew Munro, who led the research in Manchester’s Faculty of Life Sciences.
“The bacterium survives the initial attack by the body’s immune system and then lies dormant, usually in the lungs, waiting for any sign of weakness, such as a secondary infection. Its resurgence over the last 20 years has been closely associated with the AIDS epidemic, which destroys the human immune system and has allowed TB to get a grip once again.”
London is the TB capital of Europe, although most large cities here and in North America have seen rapid increases in the number of TB infections. However, the problem is most acute in Africa and Asia where HIV/AIDS is also most prolific and a shortage of traditional TB medicines and problems with patient compliance has led to the emergence of drug-resistant strains of the disease.
“There were only ever a limited number of drugs that were effective against TB anyway,” said Professor Munro, who is based in the University’s £38 million Manchester Interdisciplinary Biocentre.
“People in places like India or Africa would be given antibiotics but often not in sufficient quantities to kill the bug completely; this is how resistant strains develop and these regions have become huge breeding grounds for these ‘super strains’.”
Funded by the EU’s NM4TB (new medicines for tuberculosis) project, the Manchester team set about trying to find alternative drugs that could be used to treat these multi-drug resistant varieties of TB, known as MDR-TB.
“We knew that the TB bacterium was a clever organism, able to evade the human immune system and to survive long-term, sometimes unnoticed, in the body. We also realised that these peculiar features of the TB bacterium must mean that there are ‘unusual’ aspects of its composition and biochemistry that set it apart from most other bacteria and that could provide new targets for antibiotic drugs.
“When we began looking at the bug and its DNA content in more detail, we noticed it had some unusual characteristics. In particular, we noted the presence of a very large number of enzymes called P450s, which are usually associated with more complex organisms.
“In humans, P450s oxygenate molecules in the body and are essential for steroid metabolism; they are also prevalent in the liver where they help us detoxify and dispose of countless chemicals and toxins that enter our system. Most bacteria have few, if any, P450s but we discovered that the TB bacterium has 20 different types.”
Even more exciting for the team was the knowledge that existing anti-fungal drugs already target P450s as a way to treat, for example, systemic and more superficial infections caused by fungi such as Candida albicans (the causative agent of thrush).
“The class of drugs called azoles are able to kill off fungal infections by blocking the actions of one of its P450s that is essential for maintaining the cell structure,” said Professor Munro. “We were able to show in laboratory experiments that various types of these azole drugs were also very good at killing the TB bacterium, and also that they bind very tightly to a number of the TB P450 enzymes that we have isolated – inactivating their function.”
The research – published in the Journal of Biological Chemistry – offers the potential of a whole new approach to fighting the TB bug and has already attracted interest from one major pharmaceutical company.
Aeron Haworth | alfa
For a chimpanzee, one good turn deserves another
27.06.2017 | Max-Planck-Institut für Mathematik in den Naturwissenschaften (MPIMIS)
New method to rapidly map the 'social networks' of proteins
27.06.2017 | Salk Institute
An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.
Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...
Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.
Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...
Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.
As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...
Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.
With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...
Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine
Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...
19.06.2017 | Event News
13.06.2017 | Event News
13.06.2017 | Event News
27.06.2017 | Power and Electrical Engineering
27.06.2017 | Information Technology
27.06.2017 | Physics and Astronomy