Development of a Genome-Scale Metabolic Model and Phenome Analysis of the Probiotic Escherichia coli Strain Nissle 1917

• Published in: International journal of molecular sciences Vol. 22; no. 4; p. 2122
• Main Authors: Kim, Dohyeon, Kim, Youngshin, Yoon, Sung Ho
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 20-02-2021; MDPI
• Subjects: Acids; Anaerobic conditions; Anaerobiosis; Antibiotics; Antigens; Biosynthesis; Carbon; Carbon - pharmacology; Computer Simulation; Digestive system; DNA microarrays; Drug development; E coli; Escherichia coli; Escherichia coli - drug effects; Escherichia coli - genetics; Escherichia coli - growth & development; Escherichia coli - metabolism; Escherichia coli Nissle 1917; flux balance analysis; Genes; Genome, Bacterial; Genomes; Genotype & phenotype; Growth conditions; Inflammatory bowel diseases; Inflammatory diseases; Intestine; Intestines - microbiology; Metabolic Flux Analysis; metabolic network model; Metabolic networks; Metabolic Networks and Pathways - drug effects; Metabolic Networks and Pathways - genetics; Metabolism; Metabolites; Microbiota; Microorganisms; Models, Biological; Multigene Family; Nitrogen; Nitrogen - pharmacology; Nutrient sources; Optimization techniques; phenome analysis; Phenomics; Phenotype; Phenotypes; Probiotics; Probiotics - metabolism; Reproducibility of Results; Simulation; Sodium; Ulcerative colitis; metabolic network model; flux balance analysis; phenome analysis; Escherichia coli Nissle 1917; probiotics
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22042122

Nissle 1917 (EcN) is an intestinal probiotic that is effective for the treatment of intestinal disorders, such as inflammatory bowel disease and ulcerative colitis. EcN is a representative Gram-negative probiotic in biomedical research and is an intensively studied probiotic. However, to date, its genome-wide metabolic network model has not been developed. Here, we developed a comprehensive and highly curated EcN metabolic model, referred to as iDK1463, based on genome comparison and phenome analysis. The model was improved and validated by comparing the simulation results with experimental results from phenotype microarray tests. iDK1463 comprises 1463 genes, 1313 unique metabolites, and 2984 metabolic reactions. Phenome data of EcN were compared with those of
intestinal commensal K-12 MG1655. iDK1463 was simulated to identify the genetic determinants responsible for the observed phenotypic differences between EcN and K-12. Further, the model was simulated for gene essentiality analysis and utilization of nutrient sources under anaerobic growth conditions. These analyses provided insights into the metabolic mechanisms by which EcN colonizes and persists in the gut. iDK1463 will contribute to the system-level understanding of the functional capacity of gut microbes and their interactions with microbiota and human hosts, as well as the development of live microbial therapeutics.