title: Francisella tularensis harvests nutrients derived via ATG5-independent autophagy to support intracellular growth.
abstract: Francisella tularensis is a highly virulent intracellular pathogen that invades and replicates within numerous host cell types including macrophages, hepatocytes and pneumocytes. By 24 hours post invasion, F. tularensis replicates up to 1000-fold in the cytoplasm of infected cells. To achieve such rapid intracellular proliferation, F. tularensis must scavenge large quantities of essential carbon and energy sources from the host cell while evading anti-microbial immune responses. We found that macroautophagy, a eukaryotic cell process that primarily degrades host cell proteins and organelles as well as intracellular pathogens, was induced in F. tularensis infected cells. F. tularensis not only survived macroautophagy, but optimal intracellular bacterial growth was found to require macroautophagy. Intracellular growth upon macroautophagy inhibition was rescued by supplying excess nonessential amino acids or pyruvate, demonstrating that autophagy derived nutrients provide carbon and energy sources that support F. tularensis proliferation. Furthermore, F. tularensis did not require canonical, ATG5-dependent autophagy pathway induction but instead induced an ATG5-independent autophagy pathway. ATG5-independent autophagy induction caused the degradation of cellular constituents resulting in the release of nutrients that the bacteria harvested to support bacterial replication. Canonical macroautophagy limits the growth of several different bacterial species. However, our data demonstrate that ATG5-independent macroautophagy may be beneficial to some cytoplasmic bacteria by supplying nutrients to support bacterial growth.
authors: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors: Shaun
authors: S
authors: Steele
authors: Jason
authors: J
authors: Brunton
authors: Benjamin
authors: B
authors: Ziehr
authors: Sharon
authors: S
authors: Taft-Benz
authors: Nathaniel
authors: N
authors: Moorman
authors: Thomas
authors: T
authors: Kawula
mesh_terms: D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D001343:Autophagy; D000071187:Autophagy-Related Protein 5; D000071186:Beclin-1; D015153:Blotting, Western; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D005347:Fibroblasts / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D005604:Francisella tularensis / Q000235:genetics / Q000254:growth & development* / Q000472:pathogenicity; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D051379:Mice; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000502:physiology*; D019289:Pyruvic Acid / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014406:Tularemia / Q000235:genetics / Q000382:microbiology* / Q000473:pathology
chemical_list: D000596:Amino Acids; D051017:Apoptosis Regulatory Proteins; C495773:Atg5 protein, mouse; D000071187:Autophagy-Related Protein 5; D000071186:Beclin-1; C115010:Becn1 protein, mouse; D008869:Microtubule-Associated Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D019289:Pyruvic Acid
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