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:6/2/2016)... -- Perimeter Surveillance & Detection Systems, Biometrics ... Support & Other Service  The latest report ... analysis of the global Border Security market . ... $17.98 billion in 2016. Now: In November ... software and hardware technologies for advanced video surveillance. ...
(Date:5/20/2016)... -- VoiceIt is excited to announce its new marketing ... working together, VoiceIt and VoicePass will offer an ... slightly different approaches to voice biometrics, collaboration between ... Both companies ... "This marketing and technology partnership allows VoiceIt ...
(Date:5/9/2016)... -- Elevay is currently known as the ... high net worth professionals seeking travel for work   ... there is still no substitute for a face-to-face meeting. ... deal with a firm handshake. This is why wealthy ... citizenship via investment programs like those offered by the ...
Breaking Biology News(10 mins):
(Date:6/27/2016)... ... 27, 2016 , ... Parallel 6 , the leading software as a ... Reach Virtual Patient Encounter CONSULT module which enables both audio and video telemedicine ... team. , Using the CONSULT module, patients and physicians can schedule a face to ...
(Date:6/27/2016)... ... June 27, 2016 , ... Rolf K. Hoffmann, ... faculty of the University of North Carolina Kenan-Flagler Business School effective ... at UNC Kenan-Flagler, with a focus on the school’s international efforts, leading classes ...
(Date:6/27/2016)... Ginkgo Bioworks , a leading organism design company ... as one of the World Economic Forum,s Technology ... companies. Ginkgo Bioworks is engineering biology to manufacture ... the nutrition, health and consumer goods sectors. The ... Fortune 500 companies to design microbes for their ...
(Date:6/24/2016)... 24, 2016 Epic Sciences unveiled a ... susceptible to PARP inhibitors by targeting homologous recombination ... The new test has already been incorporated into ... cancer types. Over 230 clinical trials ... pathways, including PARP, ATM, ATR, DNA-PK and WEE-1. ...
Breaking Biology Technology: