Structural Studies May Aid Fight Against Cystic Fibrosis

Release Date:
2/7/2007
Contact:
NIGMS OCPL
301-496-7301
info@nigms.nih.gov

Disease-causing bacteria, or pathogens, often sicken people and animals by secreting toxins that interfere with nerves, muscles, blood flow, or other body functions. Studies of the elaborate microbial protein structures that deliver these toxins can yield insights for the development of new therapies.

While investigating the structures of various pathogen proteins, biophysicist Andrzej Joachimiak, Ph.D., at the Argonne National Laboratory in Illinois discovered a bagel-shaped protein from the Pseudomonas aeruginosa bacterium that looked like it might work as a channel for toxins. This microbe is known to thrive in lung mucus and is a leading cause of death in people with cystic fibrosis.

Another research group learned of Joachimiak’s findings and, seeing the protein’s amino-acid sequence, immediately recognized it as a key part of a toxin-delivery system in Vibrio cholerae, the bacterium that causes cholera. More experiments verified that many bacteria use the same protein to inject toxins into cells. The scientists discovered significant levels of the protein in the sputum of cystic fibrosis patients.

This work, funded by the National Institute of General Medical Sciences-led Protein Structure Initiative, highlights how basic structural biology studies can reveal important information about specific health conditions. The findings point to a possible drug target to fight life-threatening infections in cystic fibrosis and other diseases.