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:2/11/2016)... Solutions announces today that its license plate recognition (LPR) cameras ... Lee,s Summit Police Department to improve safety for ... homicide suspect. Kansas City , ... and is home to roughly 100,000 residents. Lee,s ... plate reader system and also leverages Vigilant,s network of commercially ...
(Date:2/10/2016)... PUNE, India , February 10, 2016 ... --> According to 2016 iris ... fingerprint identification iris recognition is more widely ... are available with both fingerprint and iris ... allows the user to avoid purchasing two ...
(Date:2/9/2016)... Feb. 9, 2016 Aware, Inc. (NASDAQ: AWRE ), ... results for its fourth quarter and year ended December 31, 2015.  ... the fourth quarter of 2015 was $6.9 million, an increase of ... Operating income in the fourth quarter of 2015 was $2.6 million ... --> --> Higher revenue and ...
Breaking Biology News(10 mins):
(Date:2/11/2016)... , February 11, 2016 ... Corporation ("PositiveID" or "Company") (OTCQB: PSID), a life ... today that its Thermomedics subsidiary, which markets the ... its growth plan in January 2016, including entering ... increasing sequential monthly sales growth, and establishing several ...
(Date:2/10/2016)... BioAmber Inc. (NYSE: BIOA ), a leader in ... Co. Ltd., its partner in the Sarnia ... additional CDN$25 million in the joint venture for 10% ... 40%.  Mitsui will also play a stronger role in ... Sarnia , providing dedicated resources alongside BioAmber,s commercial ...
(Date:2/10/2016)... (PRWEB) , ... February 10, ... ... REGN) today announced that it has joined the Human Vaccines Project, a ... infectious diseases and cancer. , The Human Vaccines Project brings together ...
(Date:2/10/2016)... MO (PRWEB) , ... February 10, 2016 , ... ... will attend the International Society of Pharmaceutical Engineering (ISPE) Rocky Mountain Chapter 21st ... ISPE is expecting to fill more than 100 tables for its annual event, ...
Breaking Biology Technology: