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 To proliferate or not to proliferate
21.03.2019 | Max-Planck-Institut für molekulare Zellbiologie und Genetik

nachricht Discovery of a Primordial Metabolism in Microbes
21.03.2019 | Leibniz-Institut DSMZ-Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Magnetic micro-boats

Nano- and microtechnology are promising candidates not only for medical applications such as drug delivery but also for the creation of little robots or flexible integrated sensors. Scientists from the Max Planck Institute for Polymer Research (MPI-P) have created magnetic microparticles, with a newly developed method, that could pave the way for building micro-motors or guiding drugs in the human body to a target, like a tumor. The preparation of such structures as well as their remote-control can be regulated using magnetic fields and therefore can find application in an array of domains.

The magnetic properties of a material control how this material responds to the presence of a magnetic field. Iron oxide is the main component of rust but also...

Im Focus: Self-healing coating made of corn starch makes small scratches disappear through heat

Due to the special arrangement of its molecules, a new coating made of corn starch is able to repair small scratches by itself through heat: The cross-linking via ring-shaped molecules makes the material mobile, so that it compensates for the scratches and these disappear again.

Superficial micro-scratches on the car body or on other high-gloss surfaces are harmless, but annoying. Especially in the luxury segment such surfaces are...

Im Focus: Stellar cartography

The Potsdam Echelle Polarimetric and Spectroscopic Instrument (PEPSI) at the Large Binocular Telescope (LBT) in Arizona released its first image of the surface magnetic field of another star. In a paper in the European journal Astronomy & Astrophysics, the PEPSI team presents a Zeeman- Doppler-Image of the surface of the magnetically active star II Pegasi.

A special technique allows astronomers to resolve the surfaces of faraway stars. Those are otherwise only seen as point sources, even in the largest telescopes...

Im Focus: Heading towards a tsunami of light

Researchers at Chalmers University of Technology and the University of Gothenburg, Sweden, have proposed a way to create a completely new source of radiation. Ultra-intense light pulses consist of the motion of a single wave and can be described as a tsunami of light. The strong wave can be used to study interactions between matter and light in a unique way. Their research is now published in the scientific journal Physical Review Letters.

"This source of radiation lets us look at reality through a new angle - it is like twisting a mirror and discovering something completely different," says...

Im Focus: Revealing the secret of the vacuum for the first time

New research group at the University of Jena combines theory and experiment to demonstrate for the first time certain physical processes in a quantum vacuum

For most people, a vacuum is an empty space. Quantum physics, on the other hand, assumes that even in this lowest-energy state, particles and antiparticles...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

International Modelica Conference with 330 visitors from 21 countries at OTH Regensburg

11.03.2019 | Event News

Selection Completed: 580 Young Scientists from 88 Countries at the Lindau Nobel Laureate Meeting

01.03.2019 | Event News

LightMAT 2019 – 3rd International Conference on Light Materials – Science and Technology

28.02.2019 | Event News

 
Latest News

To proliferate or not to proliferate

21.03.2019 | Life Sciences

Magnetic micro-boats

21.03.2019 | Physics and Astronomy

Motorless pumps and self-regulating valves made from ultrathin film

21.03.2019 | HANNOVER MESSE

VideoLinks
Science & Research
Overview of more VideoLinks >>>