Heinemann2005 - Genome-scale reconstruction of Staphylococcus aureus (iMH551)

Heinemann2005 - Genome-scale reconstruction
of Staphylococcus aureus (iMH551)

This model is described in the article:

In silico genome-scale
reconstruction and validation of the Staphylococcus aureus
metabolic network.

Heinemann M, Kümmel A,
Ruinatscha R, Panke S.
Biotechnol. Bioeng. 2005 Dec; 92(7):
850-864
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.

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