title: Genomic analysis reveals that Pseudomonas aeruginosa virulence is combinatorial.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Molecular Biology, Massachusetts General Hospital, Cambridge Street, Boston, Massachusetts 02114, USA.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Lee
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Urbach
authors.forename: Gang
authors.initials: G
authors.lastname: Wu
authors.forename: Nicole T
authors.initials: NT
authors.lastname: Liberati
authors.forename: Rhonda L
authors.initials: RL
authors.lastname: Feinbaum
authors.forename: Sachiko
authors.initials: S
authors.lastname: Miyata
authors.forename: Lenard T
authors.initials: LT
authors.lastname: Diggins
authors.forename: Jianxin
authors.initials: J
authors.lastname: He
authors.forename: Maude
authors.initials: M
authors.lastname: Saucier
authors.forename: Eric
authors.initials: E
authors.lastname: Déziel
authors.forename: Lisa
authors.initials: L
authors.lastname: Friedman
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: George
authors.initials: G
authors.lastname: Grills
authors.forename: Kate
authors.initials: K
authors.lastname: Montgomery
authors.forename: Raju
authors.initials: R
authors.lastname: Kucherlapati
authors.forename: Laurence G
authors.initials: LG
authors.lastname: Rahme
authors.forename: Frederick M
authors.initials: FM
authors.lastname: Ausubel
mesh_terms: D001483:Base Sequence; D020650:Combinatorial Chemistry Techniques / Q000379:methods; D017931:DNA Primers; D004269:DNA, Bacterial / Q000235:genetics; D016680:Genome, Bacterial; D023281:Genomics; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D011549:Pseudomonas / Q000235:genetics* / Q000472:pathogenicity*; D017422:Sequence Analysis, DNA; D014774:Virulence / Q000235:genetics*
chemical_list: D017931:DNA Primers; D004269:DNA, Bacterial