A Metabolomic View of Staphylococcus aureus and Its Ser/Thr Kinase and Phosphatase Deletion Mutants: Involvement in Cell Wall Biosynthesis

SummaryLittle is known about intracellular metabolite pools in pathogens such as Staphylococcus aureus. We have studied a particular metabolome by means of the presented LC-MS method. By investigating the central carbon metabolism which includes most of the energy transfer molecules like nucleotides, sugar mono- and biphosphates, and cofactors, a conclusion about phenotypes and stress answers in microorganisms is possible. Quantitative metabolite levels of S. aureus grown in complex lysogeny broth and in minimal medium were compared in the wild-type S. aureus strain 8325 and the isogenic eukaryotic-like protein serine/threonine kinase (ΔpknB) and phosphatase (Δstp) deletion mutants. Detection of several remarkable differences, e.g., in nucleotide metabolism and especially cell wall precursor metabolites, indicates a previously unreported importance of serine/threonine kinase/phosphatase on peptidoglycan and wall teichoic acid biosynthesis. These findings may lead to new insights into the regulation of staphylococcal cell wall metabolism.

Graphical AbstractFigure optionsDownload high-quality image (368 K)Download as PowerPoint slideHighlights
► LC-MS metabolome analysis of Staphylococcus aureus under different growth conditions reveals altered staphylococcal metabolite pools
► ΔpknB and Δstp cells show genetic depended metabolome alterations
► PknB/Stp influence central metabolic pathways and cell wall metabolism
► Peptidoglycan and wall teichoic acid synthesis is affected inverse, either by PknB or by Stp