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Adapting to clogged airways makes common pathogen resist powerful drugs
Date:2/9/2010

People with cystic fibrosis, an inherited disease that clogs airways with thick mucous, frequently have lung infections that defy treatment. While the life expectancy for children with cystic fibrosis has increased over the past few decades, many lives are still shortened in young adulthood by the ravages of lung infections.

These chronic infections are often caused by common, environmental microbes that mutate in ways that let them live and thrive in viscous lung secretions. The same adaptations also make the pathogens less likely to be killed off by powerful antibiotics, according to a recent study led by Dr. Lucas "Luke" Hoffman, University of Washington (UW) assistant professor of pediatrics.

Surprisingly, he added, the pathogens don't need any previous exposure to the antibiotics to resist their effects. The results were published in the latest edition of PLoS Pathogens.

The researchers looked at Pseudomonas aeruginosa, a microbe that can infect a cystic fibrosis patient early in life and then undergo various changes as it establishes a chronic lung infection. Pseudomonas aeruginosa with specific alterations tend to give patients a poor outcome. Some of those alterations diminish the chances of eradicating the infection with antibiotics.

It's believed that these adaptive alterations in Pseudomonas, all of which are caused by genetic changes, could be selected for by the environment inside a patient's airways, the researchers noted. Characteristics that facilitate microbial survival begin to emerge.

The specific airway conditions that select for these genetic changes, Hoffman said, remain unclear. "But," he added, "we have some clues from what is known about airway mucus."

From the point of view of Pseudomonas, the physical properties of cystic fibrosis mucus, Hoffman said, "make it a great place for the stuff people routinely breathe in to set up shop." Cysti
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Contact: Leila Gray
leilag@u.washington.edu
206-685-0381
University of Washington
Source:Eurekalert

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