Genomic analysis reveals that Pseudomonas aeruginosa virulence is combinatorial

By Daniel G. Lee, Jonathan M. Urbach, Gang Wu, Nicole T. Liberati, Rhonda L. Feinbaum, S. Miyata, L. Diggins, Jianxin He, Maude Saucier, Eric Déziel and 7 more. Genome Biology, 2006

615 citations recorded by the source corpus.

BackgroundPseudomonas 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.ResultsThe 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.ConclusionGenes 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.

Subfields: Genetics, Molecular Biology, Molecular Medicine

View Paper: https://www.semanticscholar.org/paper/a121a1a54cfe46e0e371bc0fb0de804a8ca26973

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Citations in the corpus

• Pseudomonas genomes: diverse and adaptable. (2011, background): “…sequence did aid in the identification of common P. aeruginosa virulence factors as well as PA14-specific virulence genes, but it is striking that Lee et al. (2006) concluded that it may not be possible to predict the virulence (or otherwise) of one strain based on the presence (or absence) of…”
• ADAGE-Based Integration of Publicly Available Pseudomonas aeruginosa Gene Expression Data with Denoising Autoencoders Illuminates Microbe-Host Interactions (2016, methodology): “Visual inspection of the lists of HW genes (see File S3 in the supplemental material) revealed that several nodes contained genes that are known to vary between strains (those for lipopolysaccharide [LPS], flagellin, pili, etc.) (26).”
• Pseudomonas aeruginosa population structure revisited under environmental focus (2010, background): “aeruginosa strains, once they have been occupied into a clinical habitat such as the human body, readily evolve in the due course by genetic changes in order to microevolutionary adapt to the characteristics of the human body (Lee et al., 2006; Smith et al., 2006a).”