Substrate usage determines carbon flux via the citrate cycle in Helicobacter pylori

Steiner, Thomas M.; Lettl, Clara; Schindele, Franziska; Goebel, Werner; Haas, Rainer; Fischer, Wolfgang und Eisenreich, Wolfgang (2021): Substrate usage determines carbon flux via the citrate cycle in Helicobacter pylori. In: Molecular Microbiology, Bd. 116, Nr. 3: S. 841-860

Abstract

Helicobacter pylori displays a worldwide infection rate of about 50%. The Gram-negative bacterium is the main reason for gastric cancer and other severe diseases. Despite considerable knowledge about the metabolic inventory of H. pylori, carbon fluxes through the citrate cycle (TCA cycle) remained enigmatic. In this study, different C-13-labeled substrates were supplied as carbon sources to H. pylori during microaerophilic growth in a complex medium. After growth, C-13-excess and C-13-distribution were determined in multiple metabolites using GC-MS analysis. [U-C-13(6)]Glucose was efficiently converted into glyceraldehyde but only less into TCA cycle-related metabolites. In contrast, [U-C-13(5)]glutamate, [U-C-13(4)]succinate, and [U-C-13(4)]aspartate were incorporated at high levels into intermediates of the TCA cycle. The comparative analysis of the C-13-distributions indicated an adaptive TCA cycle fully operating in the closed oxidative direction with rapid equilibrium fluxes between oxaloacetate-succinate and alpha-ketoglutarate-citrate. C-13-Profiles of the four-carbon intermediates in the TCA cycle, especially of malate, together with the observation of an isocitrate lyase activity by in vitro assays, suggested carbon fluxes via a glyoxylate bypass. In conjunction with the lack of enzymes for anaplerotic CO2 fixation, the glyoxylate bypass could be relevant to fill up the TCA cycle with carbon atoms derived from acetyl-CoA.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0950-382X
• Sprache: Englisch