Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Zooming in on the Weapons of Salmonella

04.03.2011
Bacteria like salmonellae infect their host cells by needle-shaped extensions which they create in large numbers during an attack.

A group of Vienna-based scientists headed by Thomas Marlovits employed recently developed methods of cryo-electron microscopy and have been able to clarify the structure of this infection apparatus on the near-atomic scale. The exact knowledge of the needles’ building plan may help to develop substances that interfere with its function and thus prevent infection.


Structure of the needle-complex of Salmonella, embedded in a cellular context (artist’s interpretation based on original data). IMP-IMBA


Three-dimensional reconstruction of the needle complex, the central core element of the so-called type III secretion system, which is used by many pathogens (e.g. Salmonella) to make contact with the host cell. IMP-IMBA

"Open Sesame" for bacteria

Some of the most dreaded diseases in the world such as plague, typhoid and cholera are caused by bacteria that have one thing in common: they possess an infection apparatus which is a nearly unbeatable weapon. When attacking a cell of the body, they develop numerous hollow-needle-shaped structures that project from the bacterial surface. Through these needles, the bacteria inject signal substances into the host cells, which re-program the latter and thereby overcome their defense. From this time on it's easy game for the pathogens; they can invade the cells unimpeded and in large numbers.

The biochemist and biophysicist Thomas Marlovits, a group leader at the Vienna Institutes IMP (Research Institute of Molecular Pathology) and IMBA (Institute of Molecular Biotechnology) has been occupied for several years with the infection complex of salmonellae. As early as in 2006 Thomas Marlovits showed how the needle complex of Salmonella typhimurium develops (Nature 441, 637-640). Together with his doctoral student Oliver Schraidt he has now been able to demonstrate the three-dimensional structure of this complex in extremely high resolution. The team was able to show details with dimensions of just 5 to 6 angstroems, which are nearly atomic orders of magnitude. Their work will be presented in the forthcoming issue of the journal Science.

Looks do kill!

Never before has the infection tool of salmonellae been presented in such precision. This was achieved by the combined use of high-resolution cryo-electron microscopy and specially developed imaging software. “Austria’s coolest microscope" makes it possible to shock-freeze biological samples at minus 196 degrees centigrade and view them in almost unchanged condition. However, when "zooming in" on their object, scientists are confronted with a treacherous problem: the high-energy electron beam falls at such high concentrations on the sample that the latter is destroyed after the very first image.

The Viennese scientists have resolved the problem by developing new image-processing algorithms and with sheer numbers of images. They analyzed about 37,000 images of isolated needle complexes. Similar images were grouped and computed jointly. By doing so they were able to generate a single sharp image from numerous blurred ones. This enormous computing power was created by a cluster of about 500 interconnected computers.

Microscopy without the human interference factor

The microscope works in semi-automated fashion at night to obtain the large number of images. This is very advantageous because human beings merely interfere with the job. They breathe, speak, move, and thus unsettle the sensitive microscope. Even a moving elevator may irritate the electron beam.

The cryo-electron microscope at IMP-IMBA is the only one of its kind in Austria. The immense technical effort associated with its operation pays off, as far as the scientists are concerned. Advancing into the subnanometer range created a further means of expanding their knowledge. They were able to "adjust" existing data (obtained from crystallography) to the needle structure and thus complement the three-dimensional image in a perfect manner. The use of this hybrid method enabled the scientists to elucidate the complete construction plan of the infection apparatus.

Thomas Marlovits regards this technology as an innovation boost: "Using the methods we developed for our work, we were able to establish "imaging" standards at a very high level. We can explore its absolute limits with the aid of the fantastic infrastructure we have here at Campus Vienna Biocenter."

This knowledge not only advances basic research. "Using our data, we may well be able to find a compound that interferes with the needle complex and disturb its function," says Marlovits. "We would then have a very effective medication - one that combats not only salmonellae but also other pathogens that employ this system, such as pathogens that cause cholera, plague or typhoid."

The biochemist Thomas Marlovits was born in Rechnitz, Austria. He is a joint group leader of the two institutes IMP and IMBA since 2005. Previously, he spent five years as a post-doctoral student at the University of Yale. Thomas Marlovits has been occupied with the structure and function of molecular machines. He started to investigate the infection apparatus of salmonellae at Yale and continued this work at IMP-IMBA.

Thomas Marlovits' research work is supported within the scope of "Vienna Spots of Excellence" as part of the "Center of Molecular and Cellular Nanostructure Vienna (CMCN)", headed by Thomas Marlovits. This initiative of the City of Vienna supports research projects which involve both enterprises and scientific partners.

Original paper: “Three-Dimensional Model of Salmonella’s Needle Complex at Subnanometer Resolution”. Oliver Schraidt & Thomas C. Marlovits, Science 331, pp. 1192-1195, March 4, 2011.

Dr. Heidemarie Hurtl | IMP
Further information:
http://www.imp.ac.at
http://www.imp.ac.at/contact/communications-department/press-releases/press-release/article/press-release-salmonella/articleBack/3792/

More articles from Life Sciences:

nachricht Cnidarians remotely control bacteria
21.09.2017 | Christian-Albrechts-Universität zu Kiel

nachricht Immune cells may heal bleeding brain after strokes
21.09.2017 | NIH/National Institute of Neurological Disorders and Stroke

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

Im Focus: Fast, convenient & standardized: New lab innovation for automated tissue engineering & drug

MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems Holding GmbH about commercial use of a multi-well tissue plate for automated and reliable tissue engineering & drug testing.

MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Comet or asteroid? Hubble discovers that a unique object is a binary

21.09.2017 | Physics and Astronomy

Cnidarians remotely control bacteria

21.09.2017 | Life Sciences

Monitoring the heart's mitochondria to predict cardiac arrest?

21.09.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>