title: The infectious intracellular lifestyle of Salmonella enterica relies on the adaptation to nutritional conditions within the Salmonella-containing vacuole.
abstract: Salmonella enterica serovar Typhimurium (S. Typhimurium) is a Gram-negative pathogen that causes various host-specific diseases. During their life cycle, Salmonellae survive frequent exposures to a variety of environmental stresses, e.g. carbon-source starvation. The virulence of this pathogen relies on its ability to establish a replicative niche, named Salmonella-containing vacuole, inside host cells. However, the microenvironment of the SCV and the bacterial metabolic pathways required during infection are largely undefined. In this work we developed different biological probes whose expression is modulated by the environment and the physiological state of the bacterium. We constructed transcriptional reporters by fusing promoter regions to the gfpmut3a gene to monitor the expression profile of genes involved in glucose utilization and lipid catabolism. The induction of these probes by a specific metabolic change was first tested in vitro, and then during different conditions of infection in macrophages. We were able to determine that Entner-Doudoroff is the main metabolic pathway utilized by Salmonella during infection in mouse macrophages. Furthermore, we found sub-populations of bacteria expressing genes involved in pathways for the utilization of different sources of carbon. These populations are modified in presence of different metabolizable substrates, suggesting the coexistence of Salmonella with diverse metabolic states during the infection.
authors.affiliation: a Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET), Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario , Rosario , Argentina.
authors.forename: Lautaro
authors.identifier: 0000-0002-3339-0100
authors.initials: L
authors.lastname: Diacovich
authors.affiliation: a Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET), Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario , Rosario , Argentina.
authors.forename: Lucía
authors.initials: L
authors.lastname: Lorenzi
authors.affiliation: a Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET), Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario , Rosario , Argentina.
authors.forename: Mauro
authors.initials: M
authors.lastname: Tomassetti
authors.affiliation: b Aix Marseille Université, CNRS, INSERM, CIML , Marseille , France.
authors.forename: Stéphane
authors.identifier: 0000-0001-6578-5177
authors.initials: S
authors.lastname: Méresse
authors.affiliation: a Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET), Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario , Rosario , Argentina.
authors.forename: Hugo
authors.initials: H
authors.lastname: Gramajo
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D003593:Cytoplasm / Q000382:microbiology*; D005434:Flow Cytometry; D015964:Gene Expression Regulation, Bacterial; D008264:Macrophages / Q000382:microbiology; D053858:Metabolic Networks and Pathways; D051379:Mice; D011401:Promoter Regions, Genetic; D012486:Salmonella typhimurium / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D014617:Vacuoles / Q000382:microbiology*; D014774:Virulence
chemical_list: D001426:Bacterial Proteins
keywords: Salmonella; bacteria adaptation; flow cytometric analysis; infection; metabolism; transcriptional reporters