One source of oxidative stress encountered by Pseudomonas is the antibiotic treatment that is frequently given to people who have cystic fibrosis. Antibiotics like ciprofloxacin and tobramycin kill bacteria partly by inducing the overproduction of free radicals and causing oxidative stress. Hoffman and his team found that, because these mutant microbes are resistant to oxidative stress, they were relatively resistant to these antibiotics when grown in conditions that were like cystic fibrosis mucus.

"We learned that simply by adapting to the conditions inside the airways of cystic fibrosis patients, mutated Pseudomonas can withstand the effects of ciprofloxacin and tobramycin," Hoffman said. They did not need any previous exposure to these antibiotics to reduce their susceptibility.

Hoffman and his team suspect that Pseudomonas is not the only microbe that can do this. Some of the characteristics conferred by the mutation in Pseudomonas are also exhibited in other microbes found in chronic lung infections, such as tuberculosis or the fungal pathogen, Cryptococcus neoformans, Hoffman noted. Metabolic shifts may be a way many microbes get the upper hand over their hosts - and over antibiotics.

This report, Hoffman said, may point to new ideas for treating chronic lung infections. Luckily, colonies of Pseudomonas with the lasR mutation are relatively easy to identify in hospital laboratories by their distinctive iridescent sheen. Because lasR mutant Pseudomonas has been associated with worse outcomes in cystic fibrosis patients, indentifying Pseudomonas with the lasR mutation may be of prognostic value and may indicate the need for treatment with specific antibiotics like monobactams, tetracyclines, or polymyxin, whose mode of action differs from ciprofloxacin and tobramycin. Other treatment methods may be targeted at preventing adaptive changes, such as the lasR mutation, in Pseudomonas, the researchers said.

Source: University of Washington