Reconstruction of the metabolic network of Pseudomonas aeruginosa to interrogate virulence factor synthesis

Jennifer Bartell, Anna S Blazier, Phillip Yen, Juliane Charlotte Thøgersen, Lars Jelsbak, Joanna B Goldberg, Jason A Papin

Research output: Contribution to journalJournal articleResearchpeer-review

511 Downloads (Pure)


Virulence-linked pathways in opportunistic pathogens are putative therapeutic targets that may be associated with less potential for resistance than targets in growth-essential pathways. However, efficacy of virulence-linked targets may be affected by the contribution of virulence-related genes to metabolism. We evaluate the complex interrelationships between growth and virulence-linked pathways using a genome-scale metabolic network reconstruction of Pseudomonas aeruginosa strain PA14 and an updated, expanded reconstruction of P. aeruginosa strain PAO1. The PA14 reconstruction accounts for the activity of 112 virulence-linked genes and virulence factor synthesis pathways that produce 17 unique compounds. We integrate eight published genome-scale mutant screens to validate gene essentiality predictions in rich media, contextualize intra-screen discrepancies and evaluate virulence-linked gene distribution across essentiality datasets. Computational screening further elucidates interconnectivity between inhibition of virulence factor synthesis and growth. Successful validation of selected gene perturbations using PA14 transposon mutants demonstrates the utility of model-driven screening of therapeutic targets.
Original languageEnglish
Article number14631
JournalNature Communications
Number of pages13
Publication statusPublished - 2017


Dive into the research topics of 'Reconstruction of the metabolic network of Pseudomonas aeruginosa to interrogate virulence factor synthesis'. Together they form a unique fingerprint.

Cite this