"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 EUs 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 P4
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Contact: Aeron Haworth
aeron.haworth@manchester.ac.uk
44-161-275-8383
University of Manchester
12-Mar-2007