title: Salmonella Co-opts Host Cell Chaperone-mediated Autophagy for Intracellular Growth.
abstract: Salmonella enterica are invasive intracellular pathogens that replicate within a membrane-bound compartment inside infected host cells known as the Salmonella-containing vacuole. How Salmonella obtains nutrients for growth within this intracellular niche despite the apparent isolation is currently not known. Recent studies have indicated the importance of glucose and related carbon sources for tissue colonization and intracellular proliferation within host cells during Salmonella infections, although none have been found to be essential. We found that wild-type Salmonella are capable of replicating within infected host cells in the absence of both exogenous sugars and/or amino acids. Furthermore, mutants defective in glucose uptake or dependent upon peptides for growth also showed no significant loss in intracellular replication, suggesting host-derived peptides can supply both carbon units and amino acids. Here, we show that intracellular Salmonella recruit the host proteins LAMP-2A and Hsc73, key components of the host protein turnover pathway known as chaperone-mediated autophagy involved in transport of cytosolic proteins to the lysosome for degradation. Host-derived peptides are shown to provide a significant contribution toward the intracellular growth of Salmonella The results reveal a means whereby intracellular Salmonella gain access to the host cell cytosol from within its membrane-bound compartment to acquire nutrients. Furthermore, this study provides an explanation as to how Salmonella evades activation of autophagy mechanisms as part of the innate immune response.
authors.affiliation: From the Centre for Infection Medicine, Institute of Microbiology and Epizootics, Freie Universität Berlin, 14163 Berlin, Germany.
authors.forename: Vikash
authors.initials: V
authors.lastname: Singh
authors.affiliation: From the Centre for Infection Medicine, Institute of Microbiology and Epizootics, Freie Universität Berlin, 14163 Berlin, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Finke-Isami
authors.affiliation: the Institute of Food Research, Norwich Research Park, Norwich NR4 7UA, United Kingdom.
authors.forename: Amanda C
authors.initials: AC
authors.lastname: Hopper-Chidlaw
authors.affiliation: From the Centre for Infection Medicine, Institute of Microbiology and Epizootics, Freie Universität Berlin, 14163 Berlin, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Schwerk
authors.affiliation: the Institute of Food Research, Norwich Research Park, Norwich NR4 7UA, United Kingdom.
authors.forename: Arthur
authors.initials: A
authors.lastname: Thompson
authors.affiliation: From the Centre for Infection Medicine, Institute of Microbiology and Epizootics, Freie Universität Berlin, 14163 Berlin, Germany. Electronic address: karsten.tedin@fu-berlin.de.
authors.forename: Karsten
authors.initials: K
authors.lastname: Tedin
mesh_terms: D001343:Autophagy; D045744:Cell Line, Tumor; D050883:HSC70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D054884:Host-Pathogen Interactions / Q000502:physiology*; D006801:Humans; D052119:Lysosomal-Associated Membrane Protein 2 / Q000235:genetics / Q000378:metabolism*; D012480:Salmonella Infections / Q000235:genetics / Q000378:metabolism*; D019779:Salmonella enterica / Q000502:physiology*
chemical_list: D050883:HSC70 Heat-Shock Proteins; C497811:LAMP2 protein, human; D052119:Lysosomal-Associated Membrane Protein 2
keywords: Salmonella enterica; autophagy; bacterial metabolism; bacterial pathogenesis; intracellular trafficking