Navigation Links
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 - has y ielded important clues about its activity. Qingjun Ma from Wilmanns' group purified LipB and obtained crystals of the molecule. Using the high-energy synchrotron radiation beamlines at EMBL Hamburg, on the campus of the German Electron Synchrotron Radiation Facility (DESY), he created an atom-by-atom map of the protein's structure. A high-resolution picture of the active site of LipB bound to a lipid inhibitor helped to determine the function of the enzyme. In collaboration with EMBL's Proteomics Core Facility in Heidelberg and researchers from the University of Illinois (USA), the Hamburg group discovered how LipB attaches specific fatty acids onto other proteins.

"LipB is a very promising drug target," Wilmanns says, "because it belongs to a vital pathway. Unlike other organisms M. tuberculosis has no backup mechanism that could take over LipB's role. This means that an inhibitor blocking its active site would shut down key processes the bacterium needs to survive and replicate. This would be a very effective strategy for a drug."

The scientists will now search for compounds that can do so. At the same time, they are continuing to look for other proteins as drug targets. Wilmanns and his colleagues from various other institutes are now focusing on structures of molecules that help M. tuberculosis to persist in its dormant state and could become drug targets.


'"/>

Source:European Molecular Biology Laboratory


Related biology news :

1. MetaChip provides quick, efficient toxicity screening of potential drugs
2. Simple drug has the potential to save many lives threatened by malaria
3. Scripps scientists find potential for catastrophic shifts in Pacific ecosystems
4. Engineers improve plastics potential for use in implants by linking it to biological material
5. Human embryonic stem cells have the potential to develop into eggs and sperm in the laboratory
6. Improving the potential of cancer vaccines
7. Snapin: A protein with therapy potential for autism
8. Slipping past the blood brain barrier: Research shows potential treatment for brain cancer
9. LIAI scientists make major finding on potential smallpox treatment
10. Neurotransmitters signal aggressive cancer, offer potential for early diagnosis
11. Researchers develop new testing methods for potential monkeypox or smallpox outbreak
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:6/7/2016)... , June 7, 2016  Syngrafii Inc. ... a business relationship that includes integrating Syngrafii,s patented ... branch project. This collaboration will result in greater ... the credit union, while maintaining existing document workflow ... http://photos.prnewswire.com/prnh/20160606/375871LOGO ...
(Date:6/2/2016)... --  The Weather Company , an IBM Business (NYSE: ... in which consumers will be able to interact with IBM ... voice or text and receive relevant information about the product ... have long sought an advertising solution that can create a ... and valuable; and can scale across millions of interactions and ...
(Date:5/24/2016)... facilitates superior patient care by providing unparalleled technology to leaders of the medical imaging ... product recently added to the range of products distributed by Ampronix. Photo ... ... ... News ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... , ... June 23, 2016 , ... STACS DNA Inc., ... Leader at the Arkansas State Crime Laboratory, has joined STACS DNA as a Field ... DNA team,” said Jocelyn Tremblay, President and COO of STACS DNA. “In further expanding ...
(Date:6/23/2016)... , June 23, 2016  Blueprint Bio, a company ... to the medical community, has closed its Series A ... Nunez . "We have received a commitment ... capital we need to meet our current goals," stated ... us the runway to complete validation on the current ...
(Date:6/23/2016)... ... June 23, 2016 , ... ... at the Pennsylvania Convention Center and will showcase its product’s latest features from ... also be presenting a scientific poster on Disrupting Clinical Trials in The Cloud ...
(Date:6/23/2016)...  Amgen (NASDAQ: AMGN ) today announced ... life sciences incubator to accelerate the development of new ... at QB3@953 was created to help high-potential life science ... early stage organizations - access to laboratory infrastructure. ... two "Amgen Golden Ticket" awards, providing each winner with ...
Breaking Biology Technology: