JB Accepts, published online ahead of print on 11 January 2008

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J. Bacteriol. doi:10.1128/JB.01583-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Genome-scale metabolic network analysis of the opportunistic pathogen Pseudomonas aeruginosa PAO1

Matthew A. Oberhardt, Jacek Puchaka, Kimberly E. Fryer, Vítor A.P.Martins dos Santos^*, and Jason A. Papin^*

Department of Biomedical Engineering, University of Virginia, Box 800759, Health System, Charlottesville, VA 22908, USA; Helmholtz Center for Infection Research (HZI), Inhoffenstrasse 7, D-38124 Braunschweig, Germany

^* To whom correspondence should be addressed. Email: vds{at}helmholtz-hzi.de. papin{at}virginia.edu.

Pseudomonas aeruginosa is a major life-threatening opportunistic pathogen that commonly infects immunocompromised patients. This bacterium owes its success as a pathogen largely to its metabolic versatility and flexibility. A thorough understanding of P. aeruginosa's metabolism is thus pivotal for the design of effective intervention strategies. Here we aim to provide, through systems analysis, a basis for the characterization of the genome-scale properties of this pathogens versatile metabolic network. To this end, we reconstructed a genome-scale metabolic network of Pseudomonas aeruginosa PAO1. This reconstruction accounts for 1056 genes (19% of the genome), 1030 proteins, and 883 reactions. Flux balance analysis was used to identify key features of P. aeruginosa metabolism, such as growth yield under defined conditions and knowledge gaps within the network. BIOLOG substrate oxidation data were used in model expansion, and a genome-scale transposon knockout set was compared against in silico knockout predictions to validate the model. Ultimately, this genome-scale model provides a basic modeling framework to explore the metabolism of P. aeruginosa in the context of its environmental and genetic constraints, thereby contributing to a more thorough understanding of the genotype-phenotype relationships in this resourceful and dangerous pathogen.

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