Genome-scale metabolic reconstructions of multiple Escherichia coli strains highlight strain-specific adaptations to nutritional environments

Multiple Escherichia coli genome sequences have recently been made available by advances in DNA sequencing. Analysis of these genomes has demonstrated that the fraction of genes common to all E. coli strains in the species represents a small fraction of the entire E. coli gene pool. This observation raises the question: what is a strain and what is a species? In this study, genome-scale metabolic reconstructions of multiple E. coli strains are used to reconstruct the metabolic network for an entire species and its strain-specific variants.

The models are used to determine functional differences between strains and define the E. coli species based on common metabolic capabilities. Individual strains were differentiated based on niche-specific growth capabilities. Genome-scale models (GEMs) of metabolism were constructed for 55 fully sequenced Escherichia coli and Shigella strains.

The GEMs enable a systems approach to characterizing the pan and core metabolic capabilities of the E. coli species. The majority of pan metabolic content was found to consist of alternate catabolic pathways for unique nutrient sources. The GEMs were then used to systematically analyze growth capabilities in more than 650 different growth-supporting environments.

The results show that unique strain-specific metabolic capabilities correspond to pathotypes and environmental niches. Twelve of the GEMs were used to predict growth on six differentiating nutrients, and the predictions were found to agree with 80% of experimental outcomes. Additionally, GEMs were used to predict strain-specific auxotrophies.

Twelve of the strains modeled were predicted to be auxotrophic for vitamins niacin (vitamin B3), thiamin (vitamin B1), or folate (vitamin B9). Six of the strains modeled have lost biosynthetic pathways for essential amino acids methionine, tryptophan, or leucine. Genome-scale analysis of multiple strains of a species can thus be used to define the metabolic essence of a microbial species and delineate growth differences that shed light on the adaptation process to a particular microenvironment.