Integrating highly quantitative proteomics and genome-scale metabolic modeling to study pH adaptation in the human pathogen Enterococcus faecalis

Autor: Ching-Chiek Koh, Brett G. Olivier, Ruedi Aebersold, Olga T. Schubert, Ben C. Collins, Ursula Kummer, Frank Bergmann, Madlen Strauss, Bernd Kreikemeyer, Ruth Großeholz, Tomas Fiedler, Nadine Veith
Přispěvatelé: Systems Bioinformatics, AIMMS
Rok vydání: 2016
Předmět:
Zdroj: NPJ systems biology and applications. Nature Publishing Group
npj Systems Biology and Applications, 2 (1)
Großeholz, R, Koh, C-C, Veith, N, Fiedler, T, Strauss, M, Olivier, B, Collins, B C, Schubert, O T, Bergmann, F, Kreikemeyer, B, Aebersold, R & Kummer, U 2016, ' Integrating highly quantitative proteomics and genome-scale metabolic modeling to study pH adaptation in the human pathogen Enterococcus faecalis ', npj Systems Biology and Applications, vol. 2 . https://doi.org/10.1038/npjsba.2016.17
Grosseholz, R, Ching-Chiek, K, Veith, N, Fiedler, T, Strauss, M, Olivier, B G, Collins, B C, Schubert, O T, Bergmann, F, Kreikemeyer, B, Aebersold, R & Kummer, U 2016, ' Integrating highly quantitative proteomics and genome-scale metabolic modeling to study pH adaptation in the human pathogen Enterococcus faecalis ', NPJ systems biology and applications . https://doi.org/10.1038/npjsba.2016.17
ISSN: 2056-7189
DOI: 10.1038/npjsba.2016.17
Popis: Genome-scale metabolic models represent the entirety of metabolic reactions of an organism based on the annotation of the respective genome. These models commonly allow all reactions to proceed concurrently, disregarding the fact that at no point all proteins will be present in a cell. The metabolic reaction space can be constrained to a more physiological state using experimentally obtained information on enzyme abundances. However, high-quality, genome-wide protein measurements have been challenging and typically transcript abundances have been used as a surrogate for protein measurements. With recent developments in mass spectrometry-based proteomics, exemplified by SWATH-MS, the acquisition of highly quantitative proteome-wide data at reasonable throughput has come within reach. Here we present methodology to integrate such proteome-wide data into genome-scale models. We applied this methodology to study cellular changes in Enterococcus faecalis during adaptation to low pH. Our results indicate reduced proton production in the central metabolism and decreased membrane permeability for protons due to different membrane composition. We conclude that proteomic data constrain genome-scale models to a physiological state and, in return, genome-scale models are useful tools to contextualize proteomic data.
npj Systems Biology and Applications, 2 (1)
ISSN:2056-7189
Databáze: OpenAIRE