Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Discovery of key protein’s shape could lead to improved bacterial pneumonia vaccine

22.12.2004


St. Jude finding gives insights into how pneumonia bacteria ‘hijack’ a molecular shuttle that carries antibodies from the bloodstream and use this shuttle to invade the body



Scientists at St. Jude Children’s Research Hospital have discovered that the shape of a protein on the surface of pneumonia bacteria helps these germs invade the human bloodstream. This finding, published Dec. 16 online by the EMBO Journal, could help scientists develop a vaccine that is significantly more effective at protecting children against the disease.

The St. Jude researchers determined the shape of a large, paddle-like molecule that Streptococcus pneumoniae bacteria use to latch onto cells lining the throat and lungs. The protein, called CbpA, binds to a molecule on the cell called pIgR, which takes antibodies from the bloodstream on one side of the cell and transports them to the other side. There it releases the antibody at the lining of the throat and lungs. If a pneumococcus bacterium is hovering on the lining of the respiratory tract, this germ binds to pIgR and pushes this antibody shuttle back through the cell to the bloodstream. Once at the other side of the cell, the pneumococcus breaks free of pIgR and enters the blood, where it can multiply and infect the body.


S. pneumoniae is the only bacterium known to use CbpA to invade human cells by binding to pIgR, according to Richard W. Kriwacki, Ph.D., associate member of St. Jude Structural Biology. Kriwacki is senior author of the EMBO Journal report. "The fact that we now know the structure of this important protein means we can begin to develop a vaccine that is more effective in children than those that are currently available," Kriwacki said.

Elaine Tuomanen, M.D., chair of Infectious Diseases and director of the Children’s Infection Defense Center at St. Jude, is co-author of the EMBO Journal paper.

"Using CbpA as the key part of a new vaccine against S. pneumoniae would solve a problem that now hinders our ability to protect children from this infection," Tuomanen said.

Current pneumonia vaccines designed to protect adults against more than two dozen strains of S. pneumoniae do not work in young children. Adult vaccines are composed of pieces of carbohydrates naturally appearing on the surface of these bacteria. When used in a vaccine, these pieces of carbohydrate stimulate the immune system to make antibodies against the real carbohydrate targets on the bacteria. The problem with such vaccines is that the immune systems of very young children (younger than two years) do not naturally respond to carbohydrates. Pneumococcus vaccines for children must instead be modified by binding those carbohydrates to special proteins that stimulate the immune systems of young children.

"However such vaccines are so complex that they can carry carbohydrate targets for only a few specific strains of pneumonia bacteria," Tuomanen said. "So children are always under-protected, since there are so many different strains of these bacteria."

Knowing the shape of CbpA will guide researchers in their efforts to use part or all of this protein as the basis of a vaccine against S. pneumoniae. "CbpA is a very large protein," Tuomanen said. "Now that we know what it looks like and how it’s put together, we can pull it apart to see if smaller pieces of it can be used to make a vaccine that triggers production of antibodies against the CbpA. Since all the S. pneumoniae strains need CbpA to invade the bloodstream, we can widen the protection of a vaccine to all 90 types of pneumococcus by just adding CbpA, or a piece of CbpA."

The discovery of the structure of CbpA was a two-step process that included studies of how this protein works, followed by determination of its actual structure using powerful laboratory tools.

Previous work by another team suggested that CbpA binds to pIgR. However, that finding was made in "test-tube" experiments without using actual bacteria. So the St. Jude team developed pneumococcus bacteria that had mutated CbpA in order to prove that live bacteria with mutated CbpA could not bind to pIgR on cells. "Our work confirmed that the pneumococcus uses CbpA to bind to human cells," said Beth Mann, a research laboratory specialist in Tuomanen’s lab who developed the bacteria carrying mutated CbpA. Mann, co-author of the paper, also showed that the long, paddle-shaped extensions of the protein must be folded in a specific way in order for CbpA to work.

The discovery of the actual shape of CbpA was made using nuclear magnetic resonance (NMR) spectroscopy and circular dishroism (CD). NMR combines radio wave emissions and a powerful magnetic field to determine the structure of proteins suspended in solutions, while CD measures differences in the absorption of different types of polarized light by molecules to determine their shape. It also can show how that shape can change when the protein interacts with another molecule. "This work required that we develop new NMR methods in order to determine the shape of this protein, which undergoes changes as it interacts with pIgR," said Rensheng Luo, Ph.D., a post-doctoral fellow in St. Jude Structural Biology and Infectious Diseases and first author of the paper.

Other authors of the paper are William S. Lewis, Richard Heath, Siva Sivakolundu, Eilyn R. Lacy (St. Jude); Arthur Rowe (University of Nottingham, Leicestershire, UK); Agnes E. Hamburger (California Institute of Technology, Pasadena, Calif.) and Pamela J. Bjorkman (Howard Hughes Medical Institute, California Institute of Technology).

Bonnie Cameron | EurekAlert!
Further information:
http://www.stjude.org

More articles from Life Sciences:

nachricht For a chimpanzee, one good turn deserves another
27.06.2017 | Max-Planck-Institut für Mathematik in den Naturwissenschaften (MPIMIS)

nachricht New method to rapidly map the 'social networks' of proteins
27.06.2017 | Salk Institute

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Touch Displays WAY-AX and WAY-DX by WayCon

27.06.2017 | Power and Electrical Engineering

Drones that drive

27.06.2017 | Information Technology

Ultra-compact phase modulators based on graphene plasmons

27.06.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>