New Hope for Cystic Fibrosis Patients

In a new study, researchers describe how a drug-resistant pathogenic bacterium could be surviving in the lungs of chronically infected cystic fibrosis (CF) patients, presenting a possible drug target for the disease.

Researchers from the Harvard Medical School (HMS, Boston, MA, USA) department of microbiology and molecular genetics, working with CF patients at Children's Hospital Boston (MA, USA), sought and found a protein called Hcp1 in the sputum of patients with P aeruginosa (PA), a pathogen that infects more than 80% of CF patients. They also found Hcp1 antibodies in the patients' blood, further evidence that Hcp1 plays a critical role in the infection. The study was published in the June 9, 2006, issue of Science.

Researchers at Argonne National Laboratory (ANL, Argonne, IL, USA) 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.

The amino acid sequence of Hcp1 in PA closely resembled that of Hcp1 in Vibrio cholerae, which is released from the bacterium via a novel secretion pathway. Because Hcp1 proteins from both pathogens belong to the same protein family, the researchers wondered whether the Pseudomonas Hcp1 might also be secreted via this pathway. The Harvard and Argonne researchers quickly formed a collaboration and confirmed the hypothesis. They then turned their attention to Hcp1 in CF patients to gain more insight in the role of Hcp1 during infection.

"CF patients are particularly susceptible to PA,” said lead author Dr. Joseph Mougous, of HMS. "The bacterium thrives in the excess mucus that accumulates in their lungs. Once a PA infection in a CF patient's lung has been established, these hardy bacteria are difficult or impossible to clear, which over many years eventually results in the death of the patient.”

This finding provides a possible drug target to fight the infection in cystic fibrosis patients, added Andzrej Joachimiak, director of ANL's structural biology center.



Related Links:
Harvard Medical School
Argonne National Laboratory