Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Tuberculosis bacterium is double-protected

04.03.2008
The first 3-D images that disclosure a double membrane surrounding mycobacteria were recorded by Martinsried scientists, ending a long scientific debate about the mycobacterial outer membrane and opening new pathways to improve the development of chemotherapeutic substances against tuberculosis (PNAS March, 11th, 2008; Early Online Publication).

Robert Koch who detected the tuberculosis causative agent in March 1882 described the contemporary situation: "Statistics tells us that one in seven of all humans dies of tuberculosis..."

Even today, ten million people suffer from the disease yearly, and every day, Mycobacterium tuberculosis causes the death of about 4000 patients. Medical treatment is lengthy and protection through vaccinations is, today as before, insufficient. This is why research groups worldwide study the 'acid-fast rods', which are protected by a complex and hardly penetrable cell wall. Its special structure is the reason for the resistance to external factors and for the inefficient uptake of antibacterial substances.

It has been known for some time that long-chained, strongly bound fatty acids - the mycolic acids - are necessary to preserve the resistance properties of the cell wall. But even 125 years after Koch's discovery, our knowledge of the mycobacterial cell envelope is incomplete and characterized by contradictory hypotheses. Until recently, scientists assumed that mycolic acids form a closed layer, or that they comprise the inner part of a considerably thick and asymmetrical membrane. Now, Harald Engelhardt and his group at the Max Planck Institute of Biochemistry in Martinsried have proved that the outer cell wall layer consists of a distinct lipid bilayer. Its structure, however, is hardly compatible with the current view of the cell wall architecture.

Christian Hoffman, a PhD student in Harald Engelhardt's lab, investigated the cell structure of Mycobacterium smegmatis and Mycobacterium bovis BCG, a close relative to the tuberculosis bacterium, in the electron microscope. The scientists were able to obtain 3-D images of the bilayer structure from intact cells by means of cryo-electron tomography, a technique that was developed at the institute in Martinsried. The method requires projection data from different angles of a shock-frozen cell (-190 °C) that are optimized for the number, contrast and focus of the images. In order to avoid radiation damage, the cell must only be exposed to the electron beam for a limited period of time. The images are thus noisy and lack contrast. The Department for Molecular Structural Biology, headed by Professor Wolfgang Baumeister, and in this case especially Jürgen Plitzko, pioneers development and research of cryo-electron tomography, which is a valuable technique to investigate structures of intact cells in a close-to-life state.

Hoffmann and his colleagues observed a more symmetrical and significantly thinner mycobacterial membrane than previously expected. The researchers therefore probed their results by electron microscopy of ultrathin cryosections of frozen cells (each section 35 millionth of a millimeter in thickness), which had not been treated further, and could confirm their findings. The researchers can now satisfactorily explain how the pore proteins are embedded in outer membrane of Mycobacterium smegmatis. The molecular structure of these proteins did not fit to the existing models of the mycobacterial cell wall.

Harald Engelhardt, the leader of the research project, agrees with previous hypotheses insofar as mycolic acids anchor the outer membrane to the cell wall. "But the membrane is probably not structured the way we thought. The mycolic and other fatty acids must be organized differently in the cell membrane than previously assumed." The Martinsried microbiologists and structural researchers now see the need for a more detailed study of the mycobacterial outer membrane. The recent findings provide an appropriate basis for such inquiries. Because now, distinct studies investigating the translocation of molecular substances across the outer membrane have been made possible, which should also be useful for the development of chemotherapeutic drugs. Engelhardt: "After all, the drugs must pass through cell wall as effectively as possible, and a better understanding of the mycobacterial cell envelope will certainly be helpful."

[HE/EMD]

Original Publication

Christian Hoffmann, Andrew Leis, Michael Niederweis, Jürgen M. Plitzko, and Harald Engelhardt. Disclosure of the mycobacterial outer membrane: Cryo-electron tomography and vitreous sections reveal the lipid bilayer structure.

Proceedings of the National Academy of Sciences USA, March 11th, 2008, early online publication, DOI 10.1073/pnas.0709530105)

Weitere Informationen:

Webpage of the Department Molecular Structural Biology (Head: Prof. Dr. Wolfgang Baumeister)

http://www.biochem.mpg.de/baumeister

WHO-Report No. 4: "Anti-tuberculosis drug resistance in the world"
http://www.who.int/tb/features_archive/drsreport_launch_26feb08/en/index.html
Bacteria Which Sense the Earth's Magnetic Field. Press release of the Max Planck Society, November 20th, 2005.
http://www.mpg.de/english/illustrationsDocumentation/documentation/
pressReleases/2005/pressRelease200511171/index.html

Eva-Maria Diehl | idw
Further information:
http://www.biochem.mpg.de/

Further reports about: Martinsried Mycobacterium Tuberculosis mycobacterial mycolic

More articles from Life Sciences:

nachricht Toward a 'smart' patch that automatically delivers insulin when needed
18.01.2017 | American Chemical Society

nachricht 127 at one blow...
18.01.2017 | Stiftung Zoologisches Forschungsmuseum Alexander Koenig, Leibniz-Institut für Biodiversität der Tiere

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

A big nano boost for solar cells

18.01.2017 | Power and Electrical Engineering

Glass's off-kilter harmonies

18.01.2017 | Materials Sciences

Toward a 'smart' patch that automatically delivers insulin when needed

18.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>