Discovery could aid fight against cystic fibrosis...( BOSTON June 9 2006 Harvard Medical S...)

"This work is important because pathogenic bacteria such as Pseudomonas aeruginosa (PA) use protein secretion systems to cause disease in their hosts," said Joseph Mougous, lead author of the study published in the June 9 issue of Science. "In the case of Pseudomonas aeruginosa, the host may be a cancer patient with a weakened immune system, a burn patient, or a person with cystic fibrosis (CF)."

Pseudomonas aeruginosa (PA), a pathogen that infects more than 80 percent of cystic fibrosis patients, is a leading cause of these patients' death. PA is difficult to treat because it is resistant to many drugs.

"Since we know so little about what this bacterium is up to while it's engaged in these chronic infections, the discovery of this protein secretion system might lead to finding a new target for treatments," said Mougous, a research fellow in the Harvard Medical School (HMS) Department of Microbiology and Molecular Genetics.

Researchers at Argonne National Laboratory (ANL) provided one of the clues that contributed to the HMS discovery. Working through a number of pathogenic proteins, ANL protein crystallographer Marianne Cuff saw a bagel-shaped pore that might be involved in transferring toxins into cells. She deposited the structure of the protein, called Hcp1, into the Protein Data Bank, a resource used by biologists worldwide to find information about the proteins they are studying.

While exploring the Protein Data Bank, Mougous, who was studying PA in the laboratory of department chair John Mekalanos, recognized that the amino acid sequence of Hcp1 in PA closely resembled that of Hcp1 in Vibrio cholerae. The Mekalanos lab had previously discover
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Contact: Judith Montminy
public_affairs@Hms.harvard.edu
617-432-0442
Harvard Medical School
9-Jun-2006