title: Adaptation of Bacillus subtilis carbon core metabolism to simultaneous nutrient limitation and osmotic challenge: a multi-omics perspective.
abstract: The Gram-positive bacterium Bacillus subtilis encounters nutrient limitations and osmotic stress in its natural soil ecosystem. To ensure survival and sustain growth, highly integrated adaptive responses are required. Here, we investigated the system-wide response of B. subtilis to different, simultaneously imposed stresses. To address the anticipated complexity of the cellular response networks, we combined chemostat experiments under conditions of carbon limitation, salt stress and osmoprotection with multi-omics analyses of the transcriptome, proteome, metabolome and fluxome. Surprisingly, the flux through central carbon and energy metabolism is very robust under all conditions studied. The key to achieve this robustness is the adjustment of the biocatalytic machinery to compensate for solvent-induced impairment of enzymatic activities during osmotic stress. Specifically, increased production of several enzymes of central carbon metabolism compensates for their reduced activity in the presence of high salt. A major response of the cell during osmotic stress is the production of the compatible solute proline. This is achieved through the concerted adjustment of multiple reactions around the 2-oxoglutarate node, which drives metabolism towards the proline precursor glutamate. The fine-tuning of the transcriptional and metabolic networks involves functional modules that overarch the individual pathways.
authors.affiliation: Institute of Systems Biotechnology, Saarland University, Campus A1 5, 66123, Saarbrücken, Germany; Institute of Biochemical Engineering, Braunschweig University of Technology, Braunschweig, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Kohlstedt
authors.forename: Praveen K
authors.initials: PK
authors.lastname: Sappa
authors.forename: Hanna
authors.initials: H
authors.lastname: Meyer
authors.forename: Sandra
authors.initials: S
authors.lastname: Maaß
authors.forename: Adrienne
authors.initials: A
authors.lastname: Zaprasis
authors.forename: Tamara
authors.initials: T
authors.lastname: Hoffmann
authors.forename: Judith
authors.initials: J
authors.lastname: Becker
authors.forename: Leif
authors.initials: L
authors.lastname: Steil
authors.forename: Michael
authors.initials: M
authors.lastname: Hecker
authors.forename: Jan Maarten
authors.initials: JM
authors.lastname: van Dijl
authors.forename: Michael
authors.initials: M
authors.lastname: Lalk
authors.forename: Ulrike
authors.initials: U
authors.lastname: Mäder
authors.forename: Jörg
authors.initials: J
authors.lastname: Stülke
authors.forename: Erhard
authors.initials: E
authors.lastname: Bremer
authors.forename: Uwe
authors.initials: U
authors.lastname: Völker
authors.forename: Christoph
authors.initials: C
authors.lastname: Wittmann
mesh_terms: D001412:Bacillus subtilis / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001622:Betaine / Q000378:metabolism; D050260:Carbohydrate Metabolism; D016000:Cluster Analysis; D004734:Energy Metabolism; D015964:Gene Expression Regulation, Bacterial; D064688:Metabolic Flux Analysis; D053858:Metabolic Networks and Pathways; D009997:Osmotic Pressure; D020543:Proteome / Q000235:genetics / Q000378:metabolism; D055049:Salt Tolerance; D059467:Transcriptome
chemical_list: D001426:Bacterial Proteins; D020543:Proteome; D001622:Betaine