In silico genome-scale reconstruction and validation of the Staphylococcus aureus metabolic network
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Date
2005-12
Publication Type
Journal Article
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yes
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Abstract
A genome‐scale metabolic model of the Gram‐positive, facultative anaerobic opportunistic pathogen Staphylococcus aureus N315 was constructed based on current genomic data, literature, and physiological information. The model comprises 774 metabolic processes representing approximately 23% of all protein‐coding regions. The model was extensively validated against experimental observations and it correctly predicted main physiological properties of the wild‐type strain, such as aerobic and anaerobic respiration and fermentation. Due to the frequent involvement of S. aureus in hospital‐acquired bacterial infections combined with its increasing antibiotic resistance, we also investigated the clinically relevant phenotype of small colony variants and found that the model predictions agreed with recent findings of proteome analyses. This indicates that the model is useful in assisting future experiments to elucidate the interrelationship of bacterial metabolism and resistance. To help directing future studies for novel chemotherapeutic targets, we conducted a large‐scale in silico gene deletion study that identified 158 essential intracellular reactions. A more detailed analysis showed that the biosynthesis of glycans and lipids is rather rigid with respect to circumventing gene deletions, which should make these areas particularly interesting for antibiotic development. The combination of this stoichiometric model with transcriptomic and proteomic data should allow a new quality in the analysis of clinically relevant organisms and a more rationalized system‐level search for novel drug targets. © 2005 Wiley Periodicals, Inc.
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published
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Journal / series
Volume
92 (7)
Pages / Article No.
850 - 864
Publisher
Wiley
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Edition / version
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Software
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Date collected
Date created
Subject
Staphylococcus aureus; genome-scale metabolic network; gene deletion; small colony variant
Organisational unit
03602 - Panke, Sven / Panke, Sven
Notes
Article first published online 9 September 2005, Manuscript accepted 21 June 2005, Manuscript received 30 March 2005.