Pseudomonas aeruginosa sequence reported, the biggest bacterial genome sequenced to date
Pseudomonas aeruginosa is a major cause of opportunistic human infections, due in part to its intrinsic resistance to antibiotics and disinfectants. It causes life-threatening infections in cystic fibrosis, burn, and cancer patients, as well as people breathing with assistance from ventilators. With 6.3 million base pairs and about 5,500 genes, P. aeruginosa is about a third larger than Escherichia coli, which previously was the largest bacterium to be sequenced. P. aeruginosa's large size means that it is significantly more complex and sophisticated than other bacteria, which partly explains its adaptability and intrinsic resistance to most antibiotics. The genome data now are being used in drug research to develop new classes of antibiotics active against this and related bacteria.
"We sequenced Pseudomonas to help us develop new treatments for serious lung infections," explained C. Kendall Stover, who led the research team at PathoGenesis. "We are using the genetic data to identify and validate bacterial mechanisms that could be targets for drug activity. The most promising drug compounds are those that selectively inhibit the function of genes that are essential to the bacteria but which are not shared by humans.
"Pseudomonas has become more of a problem during the past century because it is resistant to antibiotics and disinfectants that eliminate other environmental bacteria," Stover said. "Our analysis shows that Pseudomonas appears to have more regulatory genes than other bacteria, enabling it to respond more effectively to changes in its environment. It also has more 'efflux pumps' than other bacteria, enabling the bacterial cell to pump out antibiotics faster than they can enter the cell. These are molecular mechanisms that may hold promise for new drug research."
The genome sequencing phase of the project was led by researchers from the University of Washington, who determined the order and function of P. aeruginosa's DNA. Then, PathoGenesis researchers used computers to annotate and analyze the genetic data. In this phase, they identified the likely function of genome sequences by comparing them with known genes from other organisms. Genome analysis and annotation greatly benefited from the input of 61 experts in P. aeruginosa and other bacteria worldwide who corresponded via the Internet. Pseudomonas genome data were released while the project progressed, benefiting other investigators in the field before the project was completed. The final genome sequence and supplementary analyses are posted at the Pseudomonas Genome Project website (www.pseudomonas.com) and the Nature website.
PathoGenesis Corp. develops and commercializes drugs to treat chronic infectious diseases—particularly serious lung infections, including those common in cystic fibrosis, bronchiectasis, and ventilator patients. The company's first drug, TOBI (tobramycin solution for inhalation), is approved for the management of cystic fibrosis patients with P. aeruginosa lung infections.
The Cystic Fibrosis Foundation is a nonprofit voluntary health organization. Its mission is to develop the means to cure and control cystic fibrosis while improving the quality and duration of life for those with the disease today.
The University of Washington Genome Center is known for its large-scale production of genome mapping and sequencing data.
Edited by Laura DeFrancesco
Managing Editor, Bioresearch Online
Source: PathoGenesis Corp.