Dissecting the energy metabolism in Mycoplasma pneumoniae through genome‐scale metabolic modeling. Issue 1 (2nd April 2013)

• Record Type: Journal Article
• Authors: Wodke, Judith A H; Puchałka, Jacek; Lluch‐Senar, Maria; Marcos, Josep; Yus, Eva; Godinho, Miguel; Gutiérrez‐Gallego, Ricardo; dos Santos, Vitor A P Martins; Serrano, Luis; Klipp, Edda; Maier, Tobias
• Is Part Of: Molecular systems biology. Volume 9:Issue 1(2013)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2013-04-02
• Subjects: biomass composition -- energy metabolism -- in silico knock‐outs -- metabolic modeling -- Mycoplasma pneumonia; Molecular biology -- Periodicals; Systems biology -- Periodicals; 572.8
• DOI: 10.1038/msb.2013.6
• Languages: English
• ISSNs: 1744-4292

Abstract

Abstract : Mycoplasma pneumoniae, a threatening pathogen with a minimal genome, is a model organism for bacterial systems biology for which substantial experimental information is available. With the goal of understanding the complex interactions underlying its metabolism, we analyzed and characterized the metabolic network of M. pneumoniae in great detail, integrating data from different omics analyses under a range of conditions into a constraint‐based model backbone. Iterating model predictions, hypothesis generation, experimental testing, and model refinement, we accurately curated the network and quantitatively explored the energy metabolism. In contrast to other bacteria, M. pneumoniae uses most of its energy for maintenance tasks instead of growth. We show that in highly linear networks the prediction of flux distributions for different growth times allows analysis of time‐dependent changes, albeit using a static model. By performing an in silico knock‐out study as well as analyzing flux distributions in single and double mutant phenotypes, we demonstrated that the model accurately represents the metabolism of M. pneumoniae . The experimentally validated model provides a solid basis for understanding its metabolic regulatory mechanisms. Abstract : A new genome‐scale metabolic reconstruction of M. pneumonia is used in combination with external metabolite measurement and protein abundance measurements to quantitatively explore the energy metabolism of this genome‐reduce human pathogen. Synopsis: A new genome‐scale metabolic reconstruction of M. pneumonia is used in combination with external metabolite measurement and protein abundance measurements to quantitatively explore the energy metabolism of this genome‐reduce human pathogen. We established a detailed biomass composition for M. pneumoniae, thus allowing for growth simulations. Using our metabolic model, we corrected the metabolic network topology and the functional annotation of key metabolic enzymes. M. pneumoniae, unlike other laboratory‐grown bacteria, uses a high fraction of energy (up to 89%) for cellular maintenance and not for growth. Simulating different growth conditions as well as single and double mutant phenotypes, we analyzed pathway connectivity and the impact of gene deletions on the growth performance of M. pneumoniae, highlighting the limited adaptive capabilities of this minimal model organism.