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 Warming ponds could accelerate climate change
21.02.2017 | University of Exeter

nachricht An alternative to opioids? Compound from marine snail is potent pain reliever
21.02.2017 | University of Utah

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Impacts of mass coral die-off on Indian Ocean reefs revealed

21.02.2017 | Earth Sciences

Novel breast tomosynthesis technique reduces screening recall rate

21.02.2017 | Medical Engineering

Use your Voice – and Smart Homes will “LISTEN”

21.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>