Researchers identify potential new TB drug target
Chemicals found in common anti-fungal drugs could be effective at treating tuberculosis (TB), according to research from the EU-funded New Medicines for Tuberculosis (NM4TB) project. TB is caused by a bacterium called Mycobacterium tuberculosis; one third of the world's population is infected with it and it kills nearly two million people worldwide every year. The latest discovery came about thanks to a study of some of the more unusual properties of the disease. Having fought off attacks from the body's immune system, TB bacteria are able to lie dormant in the body, usually in the lungs. When the immune system is weakened, for example by HIV (Human Immunodeficiency Virus) infection, they become active again. '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,' explained Professor Andrew Munro of the University of Manchester, who led the research. '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.' One unusual feature identified by Professor Munro's team was the presence of a large number of enzymes called P450s, which are usually only found in more complex organisms. While most bacteria have few, if any, P450s, Mycobacterium tuberculosis boasts 20 different types of the enzyme. Fortunately for the researchers, drugs targeting P450s already exist, and are widely used to treat fungal infections. '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.' Subsequent work by Indian researchers revealed that the drug Econazole was effective at treating tuberculosis in mice. According to figures from the World Health Organisation, released to coincide with World TB Day on 24 March, there are signs that the global TB epidemic is levelling off. However, HIV and the spread of Extensively Drug Resistant TB (XDR TB) pose major threats to further progress in global efforts to tackle the disease. 'Because of the threat of XDR-TB, research to identify new diagnostics, drugs and vaccines is more vital than ever,' commented Dr Mario Raviglione, Director of the WHO's Stop TB Department. Figures from the EU-funded EuroTB network reveal that TB rates in the EU are currently declining at a rate of 2.5% a year; in 2005 there were just over 90,000 cases across the 27 Member States of the EU. However, rates of infection among certain groups, including those with HIV and people of foreign origin, are on the increase. Furthermore, some EU countries, particularly the Baltic States, are experiencing particularly high levels of MDR TB compared to the rest of the EU. 'Though the overall prevalence of TB in the EU is among the lowest in the world, TB among vulnerable populations in the EU has increased,' said European Health Commissioner Markos Kyprianou. 'Cooperation against this disease can save lives and prevent suffering. Targeting vulnerable groups, preventing drug-resistance, focusing more on preventive measures and remaining vigilant in countries with low incidence will be of pivotal importance in limiting the impact of TB in the EU.'