Navigation Links
Zooming in on bacterial weapons in 3-D
Date:5/21/2012

This press release is available in German.

The plague, bacterial dysentery, and cholera have one thing in common: These dangerous diseases are caused by bacteria which infect their host using a sophisticated injection apparatus. Through needle-like structures, they release molecular agents into their host cell, thereby evading the immune response. Researchers at the Max Planck Institute for Biophysical Chemistry in Gttingen in cooperation with colleagues at the Max Planck Institute for Infection Biology in Berlin and the University of Washington in Seattle (USA) have now elucidated the structure of such a needle at atomic resolution. Their findings might contribute to drug tailoring and the development of strategies which specifically prevent the infection process.

Hundreds of tiny hollow needles sticking out of the bacterial membrane it is a treacherous tool that makes pathogens causing plague or cholera so dangerous. Together with a base, embedded in the membrane, these miniature syringes constitute the so-called type III secretion system an injection apparatus through which the pathogens introduce molecular agents into their host cell. There, these substances manipulate essential metabolic processes and disable the immune defines of the infected cells. The consequences are fatal as the pathogens can now spread within the organism without hindrance. To date, traditional antibiotics are prescribed to fight the infection. However, as some bacterial strains succeed in developing resistances, researchers worldwide seek to discover more specific drugs.

The exact structure of the 60 to 80 nanometre (60 to 80 millionths of a millimetre) long and about eight nanometre wide needles has so far been unknown. Classical methods such as X-ray crystallography or electron microscopy failed or yielded wrong model structures. Not crystallisable and insoluble, the needle resisted all attempts to decode its atomic structure. Therefore Adam Lange and Stefan Becker at the Max Planck Institute for Biophysical Chemistry together with a team of physicists, biologists and chemists chose a completely novel approach. In cooperation with David Baker at the University of Washington, and Michael Kolbe at the Max Planck Institute for Infection Biology, the scientists successfully combined the production of the needle in the laboratory with solid-state NMR spectroscopy, electron microscopy, and computer modelling. The researchers deciphered the structure of the needle atom by atom and visualised its molecular architecture for the first time in the angstrom range, a resolution of less than a tenth of a millionth of a millimetre.

This required progresses in several fields. "We have made big steps forward concerning sample production as well as solid-state NMR spectroscopy," says Adam Lange. "Finally, we were also able to use one of the presently most powerful solid-state NMR spectrometers in Christian Griesinger's NMR-based Structural Biology Department at our Institute." With 20 tesla, the magnetic field of this 850 megahertz spectrometer is about 400,000 times as strong as that of the earth.

"We were surprised to see how the needles are constructed," says Lange. As expected, the needles of pathogens causing diseases as diverse as food poisoning, bacterial dysentery, or the plague show striking similarities. However, in contrast to prevailing assumptions, the similarities are found in the inner part of the needles whereas the surface is astonishingly variable. According to the scientist, this variability might be a strategy of the bacteria to evade immune recognition by the host. Changes on the surface of the needle make it difficult for the host's immune system to recognize the pathogen.

The scientists Lange, Kolbe, Becker, and their Max Planck colleagues Christian Griesinger und Arturo Zychlinsky, have focused on the bacterial injection apparatus for several years. Together with the Federal Institute for Materials Research and Testing they already showed in 2010 how bacteria assemble their miniature syringes. The discovery of their structure in atomic detail not only enables researchers to gain new insights into how these pathogens outwit their host cells, it also offers the prospect to block the syringe assembly and the delivery of the bacterial factors using tailored molecules. Such substances, referred to as antiinfectives, could act more specifically and much earlier during infection than traditional antibiotics. "Thanks to our new technique, we can produce large amounts of needles in the lab. Our aim is now to develop a high-throughput method. This will allow us to search for new agents that prevent the formation of the needle," explains Stefan Becker.


'/>"/>
Contact: Dr. Adam Lange
adla@nmr.mpibpc.mpg.de
49-551-201-2214
Max-Planck-Gesellschaft
Source:Eurekalert  

Related medicine news :

1. Fish Pedicure a Recipe for Bacterial Infection, Researchers Warn
2. University of Minnesota startup to treat challenging bacterial infection
3. Children with juvenile arthritis have higher rates of bacterial infection
4. Pharmacy Robots Linked to Bacterial Contamination of Drugs
5. Jefferson researchers mirror human response to bacterial infection and resolution in mice
6. Bacterial Strain Behind Black Death Plague Is Likely Extinct: Study
7. CDC Report Shows Bacterial Meningitis Cases on the Decline
8. Get a whiff of this: Low-cost sensor can diagnose bacterial infections
9. Antibacterial Soap Additive Accumulates in Fish: Study
10. Novel approaches to bacterial caries management: An efficacious solution in view?
11. Use of alcohol-free antibacterial mouth-rinse is associated with decrease in preterm birth
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Zooming in on bacterial weapons in 3-D
(Date:6/25/2016)... ... June 25, 2016 , ... As a lifelong Southern Californian, Dr. Omkar ... M.D from the David Geffen School of Medicine at UCLA. He trained in Internal ... complete his fellowship in hematology/oncology at the UCLA-Olive View-Cedars Sinai program where he had ...
(Date:6/25/2016)... ... ... On Friday, June 10, Van Mitchell, Secretary of the Maryland Department of Health and ... their exemplary accomplishments in worksite health promotion. , The Wellness at Work Awards took ... the BWI Marriott in Linthicum Heights. iHire was one of 42 businesses to receive ...
(Date:6/24/2016)... CA (PRWEB) , ... June 24, 2016 , ... A ... procedures that most people are unfamiliar with. The article goes on to state that ... but also many of these less common operations such as calf and cheek reduction. ...
(Date:6/24/2016)... ... ... June 19, 2016 is World Sickle Cell Observance Day. In an effort ... holistic treatments, Serenity Recovery Center of Marne, Michigan, has issued a pain ... Disease (SCD) is a disorder of the red blood cells, which can cause episodes ...
(Date:6/24/2016)... Texas (PRWEB) , ... June 24, 2016 , ... ... International Conference and Scientific Sessions in Dallas that it will receive two significant ... of the grants came as PHA marked its 25th anniversary by recognizing patients, ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... June 24, 2016   Bay Area Lyme ... Dean Center for Tick Borne Illness , ... Rehabilitation, MIT Hacking Medicine, University of California, Berkeley, ... announced the five finalists of Lyme Innovation ... More than 100 scientists, clinicians, researchers, entrepreneurs, and ...
(Date:6/24/2016)... , June 24, 2016  American Respiratory Labs (ARL), a ... now able to perform sophisticated lung assessments in patients, homes, thanks ... Inc. Patients are no longer limited to having ... PRO ® , ARL patients like Jeanne R. of ... the comfort of her own home. ...
(Date:6/24/2016)... , June 24, 2016  Arkis BioSciences, a ... invasive and more durable cerebrospinal fluid treatments, today ... The Series-A funding is led by Innova Memphis, ... and other private investors.  Arkis, new financing will ... and the market release of its in-licensed Endexo® ...
Breaking Medicine Technology: