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Journal of Bacteriology, August 2005, p. 5818-5830, Vol. 187, No. 16
0021-9193/05/$08.00+0     doi:10.1128/JB.187.16.5818-5830.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Expanded Metabolic Reconstruction of Helicobacter pylori (iIT341 GSM/GPR): an In Silico Genome-Scale Characterization of Single- and Double-Deletion Mutants

Ines Thiele,{dagger} Thuy D. Vo,{dagger} Nathan D. Price, and Bernhard Ø. Palsson*

Department of Bioengineering, University of California, San Diego, California

Received 14 December 2004/ Accepted 19 April 2005

Helicobacter pylori is a human gastric pathogen infecting almost half of the world population. Herein, we present an updated version of the metabolic reconstruction of H. pylori strain 26695 based on the revised genome annotation and new experimental data. This reconstruction, iIT341 GSM/GPR, represents a detailed review of the current literature about H. pylori as it integrates biochemical and genomic data in a comprehensive framework. In total, it accounts for 341 metabolic genes, 476 intracellular reactions, 78 exchange reactions, and 485 metabolites. Novel features of iIT341 GSM/GPR include (i) gene-protein-reaction associations, (ii) elementally and charge-balanced reactions, (iii) more accurate descriptions of isoprenoid and lipopolysaccharide metabolism, and (iv) quantitative assessments of the supporting data for each reaction. This metabolic reconstruction was used to carry out in silico deletion studies to identify essential and conditionally essential genes in H. pylori. A total of 128 essential and 75 conditionally essential metabolic genes were identified. Predicted growth phenotypes of single knockouts were validated using published experimental data. In addition, in silico double-deletion studies identified a total of 47 synthetic lethal mutants involving 67 different metabolic genes in rich medium.

* Corresponding author. Mailing address: Department of Bioengineering, University of California—San Diego, 9500 Gilman Dr. 0412, La Jolla, CA 92093-0412. Phone: (858) 534-5668. Fax: (858) 822-3120. E-mail: palsson{at}ucsd.edu.

{dagger} These authors contributed equally to this work.

Journal of Bacteriology, August 2005, p. 5818-5830, Vol. 187, No. 16
0021-9193/05/$08.00+0     doi:10.1128/JB.187.16.5818-5830.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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