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Viral DNA in bacterial genome could hold key to novel cystic fibrosis treatments

12/02/2008

December 2, 2008 The bacterium Pseudomonas aeruginosa is well known for its environmental versatility, ability to cause infection in humans, and its capacity to resist antibiotics. P. aeruginosa is the most common cause of persistent and fatal lung infections in cystic fibrosis patients. In a study published online today in Genome Research (www.genome.org), researchers have used genomic techniques to study a particularly virulent strain of P. aeruginosa, uncovering genetic clues to its success that will aid in the design of novel therapeutic strategies.

The Liverpool Epidemic Strain, the most common strain of P. aeruginosa infecting cystic fibrosis patients in the United Kingdom, is characterized by its particular aggressiveness and virulence. Though approximately 90% of the P. aeruginosa genome is shared between different strains, a team of scientist led by Dr. Craig Winstanley of the University of Liverpool set out to investigate the unique genomic features of the Liverpool strain. "We used genome sequencing to reveal the secrets of the other 10% of the genome, which is likely to include genes contributing to the success of this particular strain," said Winstanley.

The research group found that many of the genes specific to the Liverpool Epidemic Strain are positioned in clusters, some of which are prophages. A prophage is a set of viral genes that became integrated into the DNA of bacteria infected by a bacterial virus. They then engineered mutations in prophages of the Liverpool strain and tested the pathogenicity of the mutant bacteria in a rat model of chronic lung infection. "We have shown that mutations within these novel prophages and genomic islands can prevent the strain from establishing infections," Winstanley described. "This indicates that bacterial viruses may contribute to the ability of bacterial pathogens to adapt to specific environments and to the emergence of particularly successful epidemic bacterial strains."

Winstanley also explained that this work is especially important in light of the nature of P. aeruginosa lung infections that afflict cystic fibrosis patients. Once an infection has been established, antibiotic therapy is unable to eradicate the bacteria from the lungs. Since antibiotics can be of limited use, the genomic properties of the Liverpool Epidemic Strain characterized in this study will aid in the development of novel strategies for circumventing ineffective antibiotic treatments by preventing infection altogether.

Scientists from the University of Liverpool (Liverpool, UK), Simon Fraser University (Burnaby, BC), Laval University (Quebec City, QC), The Wellcome Trust Sanger Institute (Hinxton, UK), and the University of British Columbia (Vancouver, BC) contributed to this study.

This work was supported by the Wellcome Trust, the Canadian Institutes of Health Research, the Canadian Cystic Fibrosis Foundation, the US Cystic Fibrosis Foundation, the Michael Smith Foundation for Health Research, the Big Lottery Fund, and the UK Cystic Fibrosis Trust.

Media contacts:
Craig Winstanley, Ph.D. is available for more information by contacting Kate Spark, University of Liverpool Media Relations Manager (kspark@liv.ac.uk; +44-151-794-2247).

Interested reporters may obtain copies of the manuscript from Peggy Calicchia, Editorial Secretary, Genome Research (calicchi@cshl.edu; +1-516-422-4012).

About the article:
The manuscript will be published online ahead of print on December 2, 2008. Its full citation is as follows:
Winstanley, C., Langille, M.G.I., Fothergill, J.L., Kukavica-Ibrulj, I., Paradis-Bleau, C., Sanschagrin, F., Thomson, N.R., Winsor, G.L., Quail, M.A., Lennard, N., Bignell, A., Clarke, L., Seeger, K., Saunders, D., Harris, D., Parkhill, J., Hancock, R.E.W., Brinkman, F.S.L., and Levesque, R.C. Newly introduced genomic prophage islands are critical determinants of in vivo competitiveness in the Liverpool Epidemic Strain of Pseudomonas aeruginosa. Genome Res. doi:10.1101/gr.086082.108.

About Genome Research:
Genome Research (www.genome.org) is an international, continuously published, peer-reviewed journal published by Cold Spring Harbor Laboratory Press. Launched in 1995, it is one of the five most highly cited primary research journals in genetics and genomics.

About Cold Spring Harbor Laboratory Press:
Cold Spring Harbor Laboratory Press is an internationally renowned publisher of books, journals, and electronic media, located on Long Island, New York. It is a division of Cold Spring Harbor Laboratory, an innovator in life science research and the education of scientists, students, and the public. For more information, visit www.cshlpress.com.

Genome Research issues press releases to highlight significant research studies that are published in the journal.



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