Protein structure a target for vaccines and antibiotics.

2003 JUN 11 - (NewsRx.com & NewsRx.net) -- A group of researchers from the Scripps Research Institute (TSRI) has solved structures of a bacterial protein called pilin, which is required for infection by pathogens that cause human diseases like meningitis, gonorrhea, diarrheal diseases, pneumonia, and cholera.

Reporting in Molecular Cell, the TSRI group described two key structures of these pilins and discoveries about their assembly into fibrous "pili." Because a whole class of bacterial pathogens requires the assembly of pilin into the hair-like pilus filaments on their surface in order for them to move around, attach to, and infect host cells, the authors believe that this research provides essential knowledge to help scientists develop novel antibiotics and vaccines against these deadly and emerging bacterial diseases.

This work directly focuses on two such pathogens - Pseudomonas aeruginosa, which causes severe lung infections in cystic fibrosis patients, AIDS patients, and other immunocompromised individuals, and Vibrio cholerae, which causes cholera, a potentially fatal diarrheal disease that primarily afflicts people in developing countries.

"Cholera," said TSRI professor John Tainer, PhD, "is a disease that could use better vaccines."

Tainer, who is an investigator in TSRI's department of molecular biology and a member of the Skaggs Institute for Chemical Biology at TSRI, determined the atomic structure of the pilus filaments with TSRI senior research associate Lisa Craig, PhD, and three other key researchers - TSRI professor Mark Yeager, computational expert and director of graphics development at TSRI Michael Pique, and Dartmouth Medical School professor Ronald Taylor.

"If we can understand their atomic structure, we can go after developing vaccines that are highly specific," said Craig, who is first author on the paper.

The pili are used by several types of bacteria to crawl around and stick to the intestine, lung, and other mucosal surfaces, and to pick up foreign genes and DNA, bringing them aboard to potentially increase the bacteria's pathogenicity. In cholera, these pili are essential for the infection because they allow the bacteria to clump together and form a colony that protects them from the human immune response. This makes pili a good target for vaccine design, since blocking them should block the bacterium's ability ...