Fachbereich Veterinärmedizin



    Salmonella co-opts host cell chaperone-mediated autophagy for intracellular growth (2016)

    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Singh, V (WE 7)
    Finke-Isami, Johannes
    Hopper-Chidlaw, Amanda C
    Schwerk, Peter (WE 7)
    Thompson, Arthur
    Tedin, Karsten (WE 7)
    The journal of biological chemistry; 292(5) — S. 1847–1864
    ISSN: 0021-9258
    URL (Volltext): https://www.ncbi.nlm.nih.gov/pubmed/27932462
    DOI: 10.1074/jbc.M116.759456
    Pubmed: 27932462
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    Abstract / Zusammenfassung

    Salmonella enterica are invasive, intracellular pathogens which replicate within a membrane-bound compartment inside infected host cells known as the Salmonella-containing vacuole (SCV). 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 colonisation 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 (CMA) involved in transport of cytosolic proteins to the lysosome for degradation. Host-derived peptides are shown to provide a significant contribution towards 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.