Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New approach to fight tuberculosis

05.12.2014

Researchers from Würzburg and Stony Brook have found a new weak spot in the bacterium that causes tuberculosis: Blocking a specific enzyme involved in the cholesterol catabolism could disable the bacteria.

In 2012, there were around 8.6 million cases of tuberculosis worldwide resulting in 1.3 million associated deaths according to the World Health Organisation WHO. About five percent of infections were caused by multidrug-resistant pathogens, a trend that is on the rise.


Interaction of the steroid (yellow) with the FadA5 enzyme of the tuberculosis bacillus. The steroid is a good basis for developing a new inhibiting drug.

(Image: Caroline Kisker)

Scientists are therefore seeking new effective ways to tackle the tuberculosis bacteria in the future. Professor Caroline Kisker and her team have devoted their research to this topic: At the University of Würzburg’s Rudolf-Virchow-Center for Experimental Biomedicine, they are studying the bacterial enzymes to pinpoint new vulnerable points.

Enzyme-steroid interaction opens up new prospects

The Würzburg researchers are looking into the pathogens' cholesterol metabolism among others. The enzyme FadA5 is of major interest in this context as it is needed by the bacillus to keep up chronic infection. Teaming up with researchers of Stony Brook University (US), Kisker and her team have now analysed the exact structure of the enzyme – and identified a potential new target for drugs.

"We inserted a steroid molecule into the enzyme's active centre and analysed the resulting structure," the Würzburg professor explains. This finding helps to design molecules that fit exactly into the active centre and block it with the aim to completely disable the enzyme FadA5, as the research group reports in the January issue of "Structure" journal.

Drug specifically targets the bacterium

A potential problem, however, is that the human organism uses enzymes which are similar to the FadA5 from the tuberculosis bacilli. Hence, it is conceivable that a new drug not only affects the bacteria, but harms the human body as well.

Therefore, Kisker's team analysed the human enzymes, too. The result was promising: "Comparing the structures showed that it should be possible to block the bacterial enzyme specifically," the professor further. Thus, an inhibiting drug should only harm the bacteria but not the human enzymes.

"The steroid is a solid basis for us to develop new inhibiting drugs," Kisker says. To pursue this goal, she has teamed up with other work groups, including that of Professor Christoph Sotriffer of the Würzburg Pharmaceutical Chemistry Department. Their aim is to find a drug that specifically inhibits the FadA5 enzyme of the tuberculosis pathogens.

Schaefer et al.: "FadA5 a thiolase from Mycobacterium tuberculosis – a unique steroid-binding pocket reveals the potential for drug development against tuberculosis", Structure, published online, 2014, December 4, DOI: http://dx.doi.org/10.1016/j.str.2014.10.010

Contact

Prof. Dr. Caroline Kisker, Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg, Phone +49 931 31-80381, caroline.kisker@virchow.uni-wuerzburg.de

Robert Emmerich | Julius-Maximilians-Universität Würzburg
Further information:
http://www.uni-wuerzburg.de

More articles from Life Sciences:

nachricht Decoding the genome's cryptic language
27.02.2017 | University of California - San Diego

nachricht New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Safe glide at total engine failure with ELA-inside

On January 15, 2009, Chesley B. Sullenberger was celebrated world-wide: after the two engines had failed due to bird strike, he and his flight crew succeeded after a glide flight with an Airbus A320 in ditching on the Hudson River. All 155 people on board were saved.

On January 15, 2009, Chesley B. Sullenberger was celebrated world-wide: after the two engines had failed due to bird strike, he and his flight crew succeeded...

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

New pop-up strategy inspired by cuts, not folds

27.02.2017 | Materials Sciences

Sandia uses confined nanoparticles to improve hydrogen storage materials performance

27.02.2017 | Interdisciplinary Research

Decoding the genome's cryptic language

27.02.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>