Bacterial DNA Sequenced from Cystic Fibrosis Patients

The DNA from a bacterium that is the most common cause of persistent and fatal lung infections in cystic fibrosis patients has been sequenced.

Molecular technology has been utilized to characterize the organism, called Pseudomonas aeruginosa, and identify a particularly virulent strain found in chronic infections.

Scientists at the University of Liverpool, (Liverpool, UK), took samples from patient's sputum and cough swabs to understand why the infection is so aggressive in people with cystic fibrosis. They used new DNA sequencing technology to read the genetic code of the infection. The technology used can read 30 billion letters of DNA sequence per day, compared to four billion using current machines. The technology allowed the scientists to investigate the mutations of the infection in precise detail, giving them valuable information about the progress of this serious medical condition.

The scientists identified a strain, called the Liverpool Epidemic Strain (LES), that can cause aggressive infection and results in progressive lung decline. This strain is referred to as a cystic fibrosis "superbug.” They demonstrated that the greatest contribution to the extremely high levels of diversity is within individual patient sputum samples rather than between patients, and they showed correlation between greater prevalence of a virulence-related phenotype and acute pulmonary symptoms. They found that during chronic infections P. aeruginosa has the ability to mutate rapidly, resulting in extensive diversity in the bacterial population. Tests also showed that when the bacteria have an overproduction of pyocyanin, a quorum-sensing-controlled virulence factor, this could be the trigger for episodes of acute infection in patients.

Craig Winstanley, PhD, a member of the Biomedical Research Center at Liverpool University, explained that patients with LES need to be separated from others in hospitals, so that infection does not spread between cystic fibrosis patients on wards. Once established, these chronic infections can never be cleared. P. aeruginosa has the ability to diversify into hundreds of distinct subtypes, making it very difficult to decide which antibiotic to use for a successful outcome. Each cystic fibrosis patient can be infected with a diverse population of bacteria and it is therefore essential to test samples of the disease from a number of patients in order to understand how it evolves. The article was published on February 4, 2011, in the American Journal of Respiratory and Critical Care Medicine.

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