title: Generation and Validation of the iKp1289 Metabolic Model for Klebsiella pneumoniae KPPR1.
abstract: Klebsiella pneumoniae has a reputation for causing a wide range of infectious conditions, with numerous highly virulent and antibiotic-resistant strains. Metabolic models have the potential to provide insights into the growth behavior, nutrient requirements, essential genes, and candidate drug targets in these strains. Here we develop a metabolic model for KPPR1, a highly virulent strain of K. pneumoniae. We apply a combination of Biolog phenotype data and fitness data to validate and refine our KPPR1 model. The final model displays a predictive accuracy of 75% in identifying potential carbon and nitrogen sources for K. pneumoniae and of 99% in predicting nonessential genes in rich media. We demonstrate how this model is useful in studying the differences in the metabolic capabilities of the low-virulence MGH 78578 strain and the highly virulent KPPR1 strain. For example, we demonstrate that these strains differ in carbohydrate metabolism, including the ability to metabolize dulcitol as a primary carbon source. Our model makes numerous other predictions for follow-up verification and analysis.
authors.affiliation: Mathematics and Computer Science Division, Argonne National Laboratory, Argonne.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Henry
authors.affiliation: Department of Microbiology-Immunology.
authors.forename: Ella
authors.initials: E
authors.lastname: Rotman
authors.affiliation: Department of Microbiology-Immunology.
authors.forename: Wyndham W
authors.initials: WW
authors.lastname: Lathem
authors.affiliation: Department of Chemical and Biological Engineering, Northwestern University, Evanston, Illinois.
authors.forename: Keith E J
authors.initials: KE
authors.lastname: Tyo
authors.affiliation: Department of Microbiology-Immunology.|Division of Infectious Diseases, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, and.
authors.forename: Alan R
authors.initials: AR
authors.lastname: Hauser
authors.affiliation: Department of Microbiology-Immunology.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Mandel
mesh_terms: D050260:Carbohydrate Metabolism; D003470:Culture Media; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D020043:Genes, Essential; D016680:Genome, Bacterial; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D010641:Phenotype; D017422:Sequence Analysis, DNA
chemical_list: D003470:Culture Media
keywords: Biolog; Klebsiella pneumoniae KPPR1; bacteria; flux balance analysis; gap filling; metabolic model; resistance; transposon insertion sequencing