Although the life expectancy for children with cystic fibrosis (CF) has increased over the past few decades, many still die because of lung infection. Pseudomonas aeruginosa, is one such microbe that can infect a CF patient early on and then adapt in ways that make them impervious to certain antibiotics.
These alterations, caused by genetic changes, could be selected for by the environment inside a patient’s airway, although what these conditions might be is still unknown, according to Lucas R. Hoffman, MD, PhD, assistant professor of pediatrics-pulmonary division at the University of Washington, and lead author of a study examining these mutations.
Oxygen levels in mucus plugs are low, and Hoffman and his team found that some Pseudomonas strains can live in this environment—in fact, one mutation actually grows better. This mutation, lasR, consumes less oxygen and uses nitrates more efficiently. It can also handle oxidative stress caused by an imbalance of free radicals.
Ironically, one source of oxidative stress facing P. aeruginosa is the very antibiotic treatment often chosen to treat CF patients. The mechanism of action of Ciprofloxacin and tobramycin is to induce the overproduction of free radicals thereby causing oxidative stress. Because P. aeruginosa is resistant to oxidative stress, it is also resistant to these antibiotics.
The pathogens did not need any previous exposure to the antibiotics to be resistant. “We learned that simply by adapting to the conditions inside the airways of CF patients, mutated Pseudomonas can withstand the effects [of these antibiotics],” said Hoffman.
Hoffman and colleagues hypothesize that P. aeruginosa is not the only microbe that can adapt like this, saying that some of the same characteristics found in the mutation of P. aeruginosa. are also found in microbes found in other chronic lung conditions, such as tuberculosis. He suggests that his research may point to new ideas for treating chronic lung infections, such as specific antibiotics whose mode of action differs from ciprofloxacin and tobramycin. He also suggests that methods targeted at preventing adaptive changes should be investigated..