Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers identify molecular anchor that allows bacterial invasion of central nervous system

02.09.2005


Could be target to block CNS infection



A single molecular anchor that allows bacteria to invade the nervous system may hold the key to treating many types of bacterial meningitis, a University of California, San Diego (UCSD) School of Medicine study has found.

By blocking the molecule’s anchoring ability, researchers may be able to find a way to stave off the most common serious infection of the central nervous system and a major cause of childhood death and disability. The researchers’ findings appear in the September 2005 issue of the Journal of Clinical Investigation.


Kelly Doran, Ph.D, assistant professor of pediatrics, Victor Nizet, M.D., associate professor of pediatrics, and their colleagues have identified a gene that produces a fat-sugar complex, which in turn anchors a molecule called LTA (short for lipoteichoic acid), found on the bacterial cell wall. This anchoring is a necessary first step for bacteria to cross from the bloodstream into the central nervous system through an anatomical obstacle called the blood-brain barrier.

"Streptococcus, which can cause meningitis, has to penetrate the normally impermeable blood-brain barrier in order to enter the central nervous system and cause disease," said Doran. "How this happens is not well known for bacteria. We wanted to see how bacteria interact with blood-brain barrier cells to begin the process of crossing over into the nervous system."

The team began by looking for new bacterial genes that allowed them to penetrate the barrier. Through a process that involved generating and screening thousands of Streptococcus mutants in a laboratory model of the human blood-brain barrier, the researchers found that a gene called iagA (short for invasion association gene-A) played a central role.

By producing a fat-sugar complex that anchors LTA, iagA establishes a link that allows bacteria to begin making its way into the nervous system. The researchers found that removing the iagA gene from the Streptococcus inhibited bacterial interactions with the blood-brain barrier, reducing mortality rates up to 90 percent in mice.

"Mice that were infected with the normal, or wild-type, Streptococcus bacteria containing iagA died within days showing evidence of bacterial meningitis. In contrast, most of the mice survived when infected with bacteria missing the single iagA gene," Doran said. "Blocking the anchoring of LTA on the bacterial cell surface could become new a therapeutic target for preventing bacterial meningitis."

Doran and Nizet noted that the study focused on how bacteria can begin the invasion process, and that additional Streptococcus toxins and the body’s own immune response also contribute to the development of meningitis. In their ongoing efforts, the researchers are looking at all of these factors in order to paint a complete picture of how the bacteria invade the brain and spinal cord to produce this potentially devastating infection.

Bacterial meningitis must be treated quickly and aggressively with antibiotics, since up to 25 percent of affected children may die or suffer permanent cognitive deficits, cerebral palsy, blindness, deafness or seizures. Therefore, an early acting treatment would help reduce the high rates of disability and death.

"Previous studies have found that Streptococcus bacteria from infants with serious disease have significantly higher levels of LTA than bacterial strains in infants without symptoms," Nizet said. "This underscores the importance of this anchor-LTA interaction, as well as its potential importance as a drug target."

The researchers’ work was supported by the Burroughs Wellcome Fund, the American Heart Association, the Edward J. Mallinckrodt, Jr., Foundation, the United Cerebral Palsy Research Foundation and the National Institutes of Health.

Doran and Nizet’s colleagues include Erin Engelson, Arya Khosravi and Heather Maisey of UCSD; Iris Fedtke and Andreas Peschel of the University of Tübingen, Germany, and Ozlem Equils, Kathrin Michelsen, and Moshe Arditi of Cedars-Sinai Medical Center, Los Angeles.

Debra Kain | EurekAlert!
Further information:
http://www.ucsd.edu

More articles from Life Sciences:

nachricht Symbiotic bacteria: from hitchhiker to beetle bodyguard
28.04.2017 | Johannes Gutenberg-Universität Mainz

nachricht Nose2Brain – Better Therapy for Multiple Sclerosis
28.04.2017 | Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Fighting drug resistant tuberculosis – InfectoGnostics meets MYCO-NET² partners in Peru

28.04.2017 | Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

 
Latest News

Wireless power can drive tiny electronic devices in the GI tract

28.04.2017 | Medical Engineering

Ice cave in Transylvania yields window into region's past

28.04.2017 | Earth Sciences

Nose2Brain – Better Therapy for Multiple Sclerosis

28.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>