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Think of sugar and you no doubt think of sweets. But sugar does more than just leave you with a sweet taste. Certain complex sugars, known as polysaccharides, are attached to the outside of bacteria and play a role in vaccine development. “These complex sugars play an important role in talking to the outside world,” says Allen Bush, a professor of biochemistry at the University of Maryland, Baltimore County. “They interact with antibodies, creating immunity in the patient when used in a vaccine.”
Now, Bush and his colleagues have discovered the chemical structures of five key polysaccharides attached to the Streptococcus pneumoniae bacteria, the team reports this month in the Journal of Biological Chemistry.
The discovery could be especially promising for children’s health. Pneumonia vaccines commonly used for adults are composed only of polysaccharides, but those don’t work in children. Vaccines that combine a polysaccharide and a protein are more effective in children -- but to create them, drug companies need a more detailed understanding of the structure of the polysaccharides involved.
To determine the structure of the polysaccharides, Bush and his colleagues dissolved a small sample in a liquid known as heavy water that, because of its molecular properties, is heavier than regular water. The researchers then put a tiny fraction of the dissolved sample in a small tube and placed it in an instrument the size of a small subcompact car, known as an NMR, or Nuclear Magnetic Resonance, machine. Performing NMR is like doing an MRI on a molecule.
“The resulting structures were surprising,” says Bush. “We just didn’t understand a lot about polysaccharide assembly. The current technology for identifying the bacterial types relies on genetic and antigenic methods that give rise to a lot of mistakes and misleading information about their structure.”
At present there are at least ninety recognized distinct pneumococcal types, referred to as serotypes, says Bush, and the detailed chemical structures of many of them are not accurately known. With NMR, Bush says scientists can better understand these polysaccharides -- and that, he says, could make a real contribution to children’s vaccine development.