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Discoveries

Insight into common CF infection

By Joseph E. Melton, Ph.D.

The breath you'll take before you get to the end of this sentence is probably something you take for granted. Not so someone with cystic fibrosis (CF). Potentially fatal pulmonary infections with the bacterium Pseudomonas aeruginosa are common in CF patients. The reason why—long poorly understood—was recently explained by a team headed by Dartmouth physiologist Bruce Stanton, Ph.D., in a paper in the American Journal of Physiology.

CF is a lethal genetic disease caused by production of an abnormal form of a protein called cystic fibrosis transmembrane conductance regulator (CFTR), which controls chloride transport in many organ systems. Of CF's assorted symptoms, lung infections are among the most life-threatening. Inhaled bacteria are normally eliminated from the lungs after being trapped in mucus that is cleared by cilia. CF impairs this mucociliary clearance activity, allowing pathogenic bacteria to colonize the lungs.

P. aeruginosa is the most virulent pulmonary pathogen for CF patients, resulting in chronic pulmonary infections that often culminate in death from respiratory failure.

Postpone: "The longer you can postpone infection," says Stanton, "the better. Aggressive treatment of early infections with antibiotics and physical therapy can help to minimize infection."

This micrograph shows the macrocolonies of bacteria that infect CF patients' lungs.

But why is P. aeruginosa so successful in colonizing the lungs of CF patients? To answer this question, Stanton and colleagues in several other departments tested the effect of P. aeruginosa on CFTR function. They cultured epithelial cells from the airways of CF patients and of healthy subjects. In both groups, exposure to the bacteria inhibited CFTR-mediated chloride transport. Bacterial filtrates produced the same effect, suggesting that a product secreted by the bacterium rather than the bacterium itself was responsible. Thus patients with CF,

who already have greatly diminished CFTR activity and mucociliary clearance, are further compromised by infection with P. aeruginosa.

What are the clinical implications of these findings? "Pseudomonas infection complicates treatment of CF," Stanton explains. "Our findings suggest that it may be necessary to block the effect of the bacteria on CFTR before [using medication to restore] CFTR function. We are attempting to identify the bacterial product so that we can design ways to block its actions."


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