title: A Comparison of the ATP Generating Pathways Used by S. Typhimurium to Fuel Replication within Human and Murine Macrophage and Epithelial Cell Lines.
abstract: The metabolism of S. Typhimurium within infected host cells plays a fundamental role in virulence since it enables intracellular proliferation and dissemination and affects the innate immune response. An essential requirement for the intracellular replication of S. Typhimurium is the need to regenerate ATP. The metabolic route used to fulfil this requirement is the subject of the present study. For infection models we used human and murine epithelial and macrophage cell lines. The epithelial cell lines were mICc12, a transimmortalised murine colon enterocyte cell line that shows many of the characteristics of a primary epithelial cell line, and HeLa cells. The model macrophage cell lines were THP-1A human monocyte/macrophages and RAW 264.7 murine macrophages. Using a mutational approach combined with an exometabolomic analysis, we showed that neither fermentative metabolism nor anaerobic respiration play major roles in energy generation in any of the cell lines studied. Rather, we identified overflow metabolism to acetate and lactate as the foremost route by which S. Typhimurium fulfils its energy requirements.
authors.affiliation: Institute of Food Research, Norwich, NR4 7UA, United Kingdom.
authors.forename: Enriqueta
authors.initials: E
authors.lastname: Garcia-Gutierrez
authors.affiliation: Institute of Food Research, Norwich, NR4 7UA, United Kingdom.
authors.forename: Amanda C
authors.initials: AC
authors.lastname: Chidlaw
authors.affiliation: Institute of Food Research, Norwich, NR4 7UA, United Kingdom.
authors.forename: Gwenaelle
authors.initials: G
authors.lastname: Le Gall
authors.affiliation: BioTechnology Institute, University of Minnesota, St. Paul, Minnesota 55108, United States of America.
authors.forename: Steven D
authors.initials: SD
authors.lastname: Bowden
authors.affiliation: Centre for Infection Medicine, Institute of Microbiology and Epizootics, Freie Universität Berlin, 14163 Berlin, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Tedin
authors.affiliation: Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, S10 2TN, United Kingdom.
authors.forename: David J
authors.initials: DJ
authors.lastname: Kelly
authors.affiliation: Institute of Food Research, Norwich, NR4 7UA, United Kingdom.
authors.forename: Arthur
authors.initials: A
authors.lastname: Thompson
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D002460:Cell Line; D006019:Glycolysis; D006367:HeLa Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000382:microbiology*; D008264:Macrophages / Q000382:microbiology*; D053858:Metabolic Networks and Pathways / Q000502:physiology; D055432:Metabolomics; D051379:Mice; D012486:Salmonella typhimurium / Q000254:growth & development / Q000378:metabolism* / Q000502:physiology; D014451:Ubiquinone / Q000378:metabolism
chemical_list: D014451:Ubiquinone; D000255:Adenosine Triphosphate