Researchers have discovered the mechanism by which the genetic defect underlying cystic fibrosis (CF) leads to fatal bacterial colonization of the lungs. The new findings, published today in the early online edition of the Proceedings of the National Academy of Sciences, suggest that an aerosol treatment aimed at balancing pH in lung cells could be developed to stave off or delay such infections.
The most common inherited lethal disorder in Caucasians, CF stems from mutations in a gene that encodes the so-called cystic fibrosis transmembrane conductance regulator (CFTR) protein. Although scientists have known that for some time, exactly how the dysfunctional protein relates to the chronic respiratory infections that characterize the disease has remained a mystery. Enter Jens Poschet of the University of New Mexico and colleagues, who found that the defect results in the excess production of acid in lung cells. This, the team determined, prevents the cells from attaching key sugar molecules to certain proteins dotting their surfaces. The absence of those sugars, in turn, enables bacteria such as Pseudomonas aeruginosa to latch onto the cells much more easily—a prelude to infection.
Importantly, when the researchers restored normal acidity to such cells in vitro, the bacteria could no longer stick to them. "This was an exciting discovery to us, because in the test tube at least we can correct the deficiency with simple maneuvers," team member Vojo Deretic of the University of New Mexico remarks. "We already have ion pump inhibitors and antacids for treating heartburn," he adds. "If we can design similar compounds to go to the lungs, we might have a simple solution to greatly improve the health of CF patients."
Kate Wong | Scientific American
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