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To assess the role of core metabolism genes in bacterial virulence - independently of their effect on growth - we correlated the genome, the transcriptome and the pathogenicity in flies and mice of 30 fully sequenced  Pseudomonas  strains. Gene presence correlates robustly with pathogenicity differences among all  Pseudomonas  species, but not among the  P. aeruginosa  strains. However, gene expression differences are evident between highly and lowly pathogenic  P. aeruginosa  strains in multiple virulence factors and a few metabolism genes. Moreover, 16.5%, a noticeable fraction of the core metabolism genes of  P. aeruginosa  strain PA14 (compared to 8.5% of the non-metabolic genes tested), appear necessary for full virulence when mutated. Most of these virulence-defective core metabolism mutants are compromised in at least one key virulence mechanism independently of auxotrophy. A pathway level analysis of PA14 core metabolism, uncovers beta-oxidation and the biosynthesis of amino-acids, succinate, citramalate, and chorismate to be important for full virulence. Strikingly, the relative expression among  P. aeruginosa  strains of genes belonging in these metabolic pathways is indicative of their pathogenicity. Thus,  P. aeruginosa  strain-to-strain virulence variation, remains largely obscure at the genome level, but can be dissected at the pathway level via functional transcriptomics of core metabolism.

Pseudomonas aeruginosa core metabolism exerts a widespread growth-independent control on virulence