title: Nutritional and metabolic requirements for the infection of HeLa cells by Salmonella enterica serovar Typhimurium.
abstract: Salmonella is the causative agent of a spectrum of human and animal diseases ranging from gastroenteritis to typhoid fever. It is a food--and water--borne pathogen and infects via ingestion followed by invasion of intestinal epithelial cells and phagocytic cells. In this study we employed a mutational approach to define the nutrients and metabolic pathways required by Salmonella enterica serovar Typhimurium during infection of a human epithelial cell line (HeLa). We deleted the key glycolytic genes, pfkA and pfkB to show that S. Typhimurium utilizes glycolysis for replication within HeLa cells; however, glycolysis was not absolutely essential for intracellular replication. Using S. Typhimurium strains deleted for genes encoding components of the phosphotransferase system and glucose transport, we show that glucose is a major substrate required for the intracellular replication of S. Typhimurium in HeLa cells. We also deleted genes encoding enzymes involved in the utilization of gluconeogenic substrates and the glyoxylate shunt and show that neither of these pathways were required for intracellular replication of S. Typhimurium within HeLa cells.
authors.affiliation: Institute of Food Research, Norwich Research Park, Colney, Norwich, United Kingdom; Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara, Japan.
authors.forename: Steven D
authors.initials: SD
authors.lastname: Bowden
authors.affiliation: Institute of Food Research, Norwich Research Park, Colney, Norwich, United Kingdom.
authors.forename: Amanda C
authors.initials: AC
authors.lastname: Hopper-Chidlaw
authors.affiliation: Institute of Food Research, Norwich Research Park, Colney, Norwich, United Kingdom.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Rice
authors.affiliation: Institute of Food Research, Norwich Research Park, Colney, Norwich, United Kingdom; Department of Plant Sciences, University of Oxford, Oxford, United Kingdom.
authors.forename: Vinoy K
authors.initials: VK
authors.lastname: Ramachandran
authors.affiliation: Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, United Kingdom.
authors.forename: David J
authors.initials: DJ
authors.lastname: Kelly
authors.affiliation: Institute of Food Research, Norwich Research Park, Colney, Norwich, United Kingdom.
authors.forename: Arthur
authors.initials: A
authors.lastname: Thompson
mesh_terms: D001692:Biological Transport; D004847:Epithelial Cells / Q000382:microbiology*; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D006367:HeLa Cells; D006801:Humans; D008954:Models, Biological; D012486:Salmonella typhimurium / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D059467:Transcriptome; D014774:Virulence / Q000235:genetics