title: Staphylococcus aureus physiological growth limitations: insights from flux calculations built on proteomics and external metabolite data.
abstract: Comparing proteomics and metabolomics allows insights into Staphylococcus aureus physiological growth. We update genome and proteome information and deliver strain-specific metabolic models for three S. aureus strains (COL, N315, and Newman). We find a number of differences in metabolism and enzymes. Growth experiments (glucose or combined with oxygen limitation) were conducted to measure external metabolites. Fluxes of the central metabolism were calculated from these data with low error. In exponential phase, glycolysis is active and amino acids are used for growth. In later phases, dehydroquinate synthetase is suppressed and acetate metabolism starts. There are strain-specific differences for these phases. A time series of 2-D gel protein expression data on COL strain delivered a second data set (glucose limitation) on which fluxes were calculated. The comparison with the metabolite-predicted fluxes shows, in general, good correlation. Outliers point to different regulated enzymes for S. aureus COL under these limitations. In exponential growth, there is lower activity for some enzymes in upper glycolysis and pentose phosphate pathway and stronger activity for some in lower glycolysis. In transition phase, aspartate kinase is expressed to meet amino acid requirements and in later phases there is high expression of glyceraldehyde-3-phosphate dehydrogenase and lysine synthetase. Central metabolite fluxes and protein expression of their enzymes correlate in S. aureus.
authors.affiliation: Department of Bioinformatics, Biocenter, University of Würzburg, Würzburg, Germany. liang@biozentrum.uni-wuerzburg.de
authors.forename: Chunguang
authors.initials: C
authors.lastname: Liang
authors.forename: Manuel
authors.initials: M
authors.lastname: Liebeke
authors.forename: Roland
authors.initials: R
authors.lastname: Schwarz
authors.forename: Daniela
authors.initials: D
authors.lastname: Zühlke
authors.forename: Stephan
authors.initials: S
authors.lastname: Fuchs
authors.forename: Leonhard
authors.initials: L
authors.lastname: Menschner
authors.forename: Susanne
authors.initials: S
authors.lastname: Engelmann
authors.forename: Christiane
authors.initials: C
authors.lastname: Wolz
authors.forename: Sarah
authors.initials: S
authors.lastname: Jaglitz
authors.forename: Jörg
authors.initials: J
authors.lastname: Bernhardt
authors.forename: Michael
authors.initials: M
authors.lastname: Hecker
authors.forename: Michael
authors.initials: M
authors.lastname: Lalk
authors.forename: Thomas
authors.initials: T
authors.lastname: Dandekar
mesh_terms: D000465:Algorithms; D001426:Bacterial Proteins / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D020869:Gene Expression Profiling; D006019:Glycolysis; D055432:Metabolomics; D008954:Models, Biological; D010427:Pentose Phosphate Pathway; D040901:Proteomics / Q000379:methods*; D013211:Staphylococcus aureus / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D049490:Systems Biology / Q000379:methods*
chemical_list: D001426:Bacterial Proteins