35 research outputs found
Quantitation of Immunoglobulins Produced by Donor Lymphocytes in Transplant Patients and the Possible Identification of Donor Cell-Produced Antiviral Antibodies by Imprint Immunofixation
The presence of β2 microglobulin on the membrane of the keratinocyte in premalignant skin disorders
Loss of β2 microglobulin from the cell surface of cutaneous malignant and premalignant lesions
Dissociation of HLA heavy chain and light chain (β2 microglobulin) expression on the cell surface of cutaneous malignancies
Using a genome-scale metabolic model of Enterococcus faecalis V583 to assess amino acid uptake and its impact on central metabolism
Increasing antibiotic resistance in pathogenic bacteria necessitates the development of new medication strategies. Interfering with the metabolic network of the pathogen can provide novel drug targets but simultaneously requires a deeper and more detailed organism-specific understanding of the metabolism, which is often surprisingly sparse. In light of this, we reconstructed a genome-scale metabolic model of the pathogen Enterococcus faecalis V583. The manually curated metabolic network comprises 642 metabolites and 706 reactions. We experimentally determined metabolic profiles of E. faecalis grown in chemically defined medium in an anaerobic chemostat setup at different dilution rates and calculated the net uptake and product fluxes to constrain the model. We computed growth-associated energy and maintenance parameters and studied flux distributions through the metabolic network. Amino acid auxotrophies were identified experimentally for model validation and revealed seven essential amino acids. In addition, the important metabolic hub of glutamine/glutamate was altered by constructing a glutamine synthetase knockout mutant. The metabolic profile showed a slight shift in the fermentation pattern toward ethanol production and increased uptake rates of multiple amino acids, especially L-glutamine and L-glutamate. The model was used to understand the altered flux distributions in the mutant and provided an explanation for the experimentally observed redirection of the metabolic flux. We further highlighted the importance of gene-regulatory effects on the redirection of the metabolic fluxes upon perturbation. The genome-scale metabolic model presented here includes gene-protein-reaction associations, allowing a further use for biotechnological applications, for studying essential genes, proteins, or reactions, and the search for novel drug targets