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New potential drug target in tuberculosis

Tuberculosis remains one of the deadliest threats to public health. Every year two million people die of the disease, which is caused by the microorganism Mycobacterium tuberculosis. Roughly one third of the world's population is infected and more and more bacterial strains have developed resistance to drugs. Researchers from the Hamburg Outstation of the European Molecular Biology Laboratory (EMBL) and the Max Planck Institute for Infection Biology (MPIIB) in Berlin have now obtained a structural image of a protein that the bacterium needs for survival in human cells. This image reveals features of the molecule that could be targeted by new antibiotic drugs. The results appear in this week's online issue of the Proceedings of the National Academy of Sciences (PNAS).

M. tuberculosis is dangerous because it hides and persists in the immune cells of our bodies. "It can only persist there because of the activity of key molecules," says Matthias Wilmanns, Head of EMBL Hamburg. "We are investigating the functions of tuberculosis proteins and determining their atomic structures, in hopes of finding weak points and new inhibitors."

A protein called LipB is essential for the organism because it activates cellular machines that drive the bacterium's metabolism. Stefan Kaufmann's department at the MPIIB has specialised in the biology of M. tuberculosis infection and its ability to survive in immune cells. They discovered that LipB is highly active in acutely infected cells, particularly in patients infected by multidrug-resistant forms of M. tuberculosis.

"In these cells we see a 70-fold increase in the production of LipB when compared to other cells," says Stefan Kaufmann, Director at the MPIIB. "This strongly indicates an involvement in pathogenesis and makes it a particularly interesting target where traditional drugs have lost their efficacy."

A structural picture of the protein - a kind of technical diagram of its building plan - h
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Contact: Anna-Lynn Wegener
wegener@embl.de
49-622-138-7452
European Molecular Biology Laboratory
29-May-2006


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