title: Metabolic adaptation of Chlamydia trachomatis to mammalian host cells.
abstract: Metabolic adaptation is a key feature for the virulence of pathogenic intracellular bacteria. Nevertheless, little is known about the pathways in adapting the bacterial metabolism to multiple carbon sources available from the host cell. To analyze the metabolic adaptation of the obligate intracellular human pathogen Chlamydia trachomatis, we labeled infected HeLa or Caco-2 cells with13C-marked glucose, glutamine, malate or a mix of amino acids as tracers. Comparative GC-MS-based isotopologue analysis of protein-derived amino acids from the host cell and the bacterial fraction showed that C. trachomatis efficiently imported amino acids from the host cell for protein biosynthesis. FT-ICR-MS analyses also demonstrated that label from exogenous13C-glucose was efficiently shuffled into chlamydial lipopolysaccharide probably via glucose 6-phosphate of the host cell. Minor fractions of bacterial Ala, Asp, and Glu were made de novo probably using dicarboxylates from the citrate cycle of the host cell. Indeed, exogenous13C-malate was efficiently taken up by C. trachomatis and metabolized into fumarate and succinate when the bacteria were kept in axenic medium containing the malate tracer. Together, the data indicate co-substrate usage of intracellular C. trachomatis in a stream-lined bipartite metabolism with host cell-supplied amino acids for protein biosynthesis, host cell-provided glucose 6-phosphate for cell wall biosynthesis, and, to some extent, one or more host cell-derived dicarboxylates, e.g. malate, feeding the partial TCA cycle of the bacterium. The latter flux could also support the biosynthesis of meso-2,6-diaminopimelate required for the formation of chlamydial peptidoglycan.
authors.affiliation: Department of Microbiology, University of Würzburg, Biocenter, Am Hubland, Würzburg, D-97074, Germany.
authors.forename: Adrian
authors.initials: A
authors.lastname: Mehlitz
authors.affiliation: Technische Universität München, Chair of Biochemistry, Lichtenbergstr. 4, Garching, D-85745, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Eylert
authors.affiliation: Technische Universität München, Chair of Biochemistry, Lichtenbergstr. 4, Garching, D-85745, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Huber
authors.affiliation: Research Center Borstel, Leibniz-Center for Medicine and Biosciences, Bioanalytical Chemistry, Borstel, D-23845, Germany.
authors.forename: Buko
authors.initials: B
authors.lastname: Lindner
authors.affiliation: Department of Microbiology, University of Würzburg, Biocenter, Am Hubland, Würzburg, D-97074, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Vollmuth
authors.affiliation: Department of Microbiology, University of Würzburg, Biocenter, Am Hubland, Würzburg, D-97074, Germany.
authors.forename: Karthika
authors.initials: K
authors.lastname: Karunakaran
authors.affiliation: Ludwig Maximilian University of Munich, Max von Pettenkofer-Institute, Pettenkoferstr. 9A, München, D-80336, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Goebel
authors.affiliation: Technische Universität München, Chair of Biochemistry, Lichtenbergstr. 4, Garching, D-85745, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Eisenreich
authors.affiliation: Department of Microbiology, University of Würzburg, Biocenter, Am Hubland, Würzburg, D-97074, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Rudel
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology*; D000596:Amino Acids / Q000378:metabolism; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D002473:Cell Wall / Q000378:metabolism*; D002692:Chlamydia trachomatis / Q000254:growth & development* / Q000378:metabolism*; D002952:Citric Acid Cycle / Q000502:physiology; D008401:Gas Chromatography-Mass Spectrometry; D005947:Glucose / Q000378:metabolism; D019298:Glucose-6-Phosphate / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D008070:Lipopolysaccharides / Q000378:metabolism; D008293:Malates / Q000378:metabolism; D010457:Peptidoglycan / Q000096:biosynthesis*
chemical_list: D000596:Amino Acids; D008070:Lipopolysaccharides; D008293:Malates; D010457:Peptidoglycan; D005973:Glutamine; D019298:Glucose-6-Phosphate; C030298:malic acid; D005947:Glucose