Genomic analysis reveals that Pseudomonas aeruginosa virulence is combinatorial

Daniel G Lee¹^,2^,3 , Jonathan M Urbach¹^,2 , Gang Wu¹^,2 , Nicole T Liberati¹^,2 , Rhonda L Feinbaum¹^,2 , Sachiko Miyata¹^,2 , Lenard T Diggins⁴ , Jianxin He⁵^,6 , Maude Saucier⁵^,6^,7 , Eric Déziel⁵^,6^,8 , Lisa Friedman⁵^,9 , Li Li¹⁰ , George Grills¹⁰^,11 , Kate Montgomery¹⁰ , Raju Kucherlapati¹⁰ , Laurence G Rahme⁵^,6 and Frederick M Ausubel¹^,2

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

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

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

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

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

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

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

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

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

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

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

author email corresponding author email

Genome Biology 2006, 7:R90doi:10.1186/gb-2006-7-10-r90


Published:	12 October 2006

Subject areas: Microbiology and parasitology, Genome studies

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.