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Genomic analysis reveals that Pseudomonas aeruginosa virulence is combinatorial

Daniel G Lee123, Jonathan M Urbach12, Gang Wu12, Nicole T Liberati12, Rhonda L Feinbaum12, Sachiko Miyata12, Lenard T Diggins4, Jianxin He56, Maude Saucier567, Eric Déziel568, Lisa Friedman59, Li Li10, George Grills1011, Kate Montgomery10, Raju Kucherlapati10, Laurence G Rahme56 and Frederick M Ausubel12*

Author Affiliations

1 Department of Molecular Biology, Massachusetts General Hospital, Cambridge Street, Boston, Massachusetts, 02114, USA

2 Department of Genetics, Harvard Medical School, Avenue Louis Pasteur, Boston, Massachusetts, 02115, USA

3 Current address: Microbia, Inc., Bent Street, Cambridge, Massachusetts, 02141, USA

4 Envivo Pharmaceuticals, Inc., Arsenal Street, Watertown, Massachusetts, 02472, USA

5 Department of Microbiology and Molecular Genetics, Harvard Medical School, Longwood Avenue, Boston, Massachusetts, 02115. USA

6 Department of Surgery, Massachusetts General Hospital, Fruit Street, Boston, Massachusetts, 02114, USA

7 Current address: Université de Montréal, Station Centre-ville, Montréal, H3C 3J7, Canada

8 Current address: INRS-Institut Armand-Frappier, boul. des Prairies, Laval, Quebec, H7V 1B7, Canada

9 Current address: Cubist Pharmaceuticals, Inc., Hayden Avenue, Lexington, Massachusetts, 02421, USA

10 Harvard Medical School - Partners Healthcare Center for Genetics and Genomics, Landsdowne Street, Cambridge, Massachusetts, 02139, USA

11 Current address: Core Facilities, Cornell University, Thurston Avenue, Ithaca, New York, 14850, USA

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Genome Biology 2006, 7:R90  doi:10.1186/gb-2006-7-10-r90

Published: 12 October 2006

Abstract

Background

Pseudomonas aeruginosa is a ubiquitous environmental bacterium and an important opportunistic human pathogen. Generally, the acquisition of genes in the form of pathogenicity islands distinguishes pathogenic isolates from nonpathogens. We therefore sequenced a highly virulent strain of P. aeruginosa, PA14, and compared it with a previously sequenced (and less pathogenic) strain, PAO1, to identify novel virulence genes.

Results

The PA14 and PAO1 genomes are remarkably similar, although PA14 has a slightly larger genome (6.5 megabses [Mb]) than does PAO1 (6.3 Mb). We identified 58 PA14 gene clusters that are absent in PAO1 to determine which of these genes, if any, contribute to its enhanced virulence in a Caenorhabditis elegans pathogenicity model. First, we tested 18 additional diverse strains in the C. elegans model and observed a wide range of pathogenic potential; however, genotyping these strains using a custom microarray showed that the presence of PA14 genes that are absent in PAO1 did not correlate with the virulence of these strains. Second, we utilized a full-genome nonredundant mutant library of PA14 to identify five genes (absent in PAO1) required for C. elegans killing. Surprisingly, although these five genes are present in many other P. aeruginosa strains, they do not correlate with virulence in C. elegans.

Conclusion

Genes required for pathogenicity in one strain of P. aeruginosa are neither required for nor predictive of virulence in other strains. We therefore propose that virulence in this organism is both multifactorial and combinatorial, the result of a pool of pathogenicity-related genes that interact in various combinations in different genetic backgrounds.