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Abstract

The gram-negative bacterial pathogen creates a novel organelle inside of eukaryotic host cells that supports intracellular replication. The –containing vacuole evades fusion with lysosomes and interacts intimately with the host endoplasmic reticulum (ER). Although the natural hosts for are free-living protozoa that reside in freshwater environments, the mechanisms that enable this pathogen to replicate intracellularly also function when mammalian macrophages phagocytose aerosolized bacteria, and infection of humans by can result in a severe pneumonia called Legionnaires' disease. A bacterial type IVB secretion system called Dot/Icm is essential for intracellular replication of . The Dot/Icm apparatus delivers over 300 different bacterial proteins into host cells during infection. These bacterial proteins have biochemical activities that target evolutionarily conserved host factors that control membrane transport processes, which results in the formation of the ER-derived vacuole that supports replication. This review highlights research discoveries that have defined interactions between vacuoles containing and the host ER. These studies reveal how creates a vacuole that supports intracellular replication by subverting host proteins that control biogenesis and fusion of early secretory vesicles that exit the ER and host proteins that regulate the shape and dynamics of the ER. In addition to recruiting ER-derived membranes for biogenesis of the vacuole in which replicates, these studies have revealed that this pathogen has a remarkable ability to interfere with the host's cellular process of autophagy, which is an ancient cell autonomous defense pathway that utilizes ER-derived membranes to target intracellular pathogens for destruction. Thus, this intracellular pathogen has evolved multiple mechanisms to control membrane transport processes that center on the involvement of the host ER.

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2016-09-08
2024-04-19
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Literature Cited

  1. Amer AO, Byrne BG, Swanson MS. 1.  2005. Macrophages rapidly transfer pathogens from lipid raft vacuoles to autophagosomes. Autophagy 153–58
  2. Amer AO, Swanson MS. 2.  2005. Autophagy is an immediate macrophage response to Legionella pneumophila. Cell Microbiol 7765–78
  3. Arasaki K, Toomre DK, Roy CR. 3.  2012. The Legionella pneumophila effector DrrA is sufficient to stimulate SNARE-dependent membrane fusion. Cell Host Microbe 1146–57
  4. Backert S, Meyer TF. 4.  2006. Type IV secretion systems and their effectors in bacterial pathogenesis. Curr. Opin. Microbiol. 9207–17
  5. Banga S, Gao P, Shen X, Fiscus V, Zong WX. 5.  et al. 2007. Legionella pneumophila inhibits macrophage apoptosis by targeting pro-death members of the Bcl2 protein family. PNAS 1045121–26
  6. Barrabeig I, Rovira A, Garcia M, Oliva JM, Vilamala A. 6.  et al. 2010. Outbreak of Legionnaires' disease associated with a supermarket mist machine. Epidemiol. Infect. 1381823–28
  7. Berger KH, Isberg RR. 7.  1993. Two distinct defects in intracellular growth complemented by a single genetic locus in Legionella pneumophila. Mol. Microbiol. 77–19
  8. Blatt SP, Parkinson MD, Pace E, Hoffman P, Dolan D. 8.  et al. 1993. Nosocomial Legionnaires' disease: Aspiration as a primary mode of disease acquisition. Am. J. Med. 9516–22
  9. Bollin GE, Plouffe JF, Para MF, Hackman B. 9.  1985. Aerosols containing Legionella pneumophila generated by shower heads and hot-water faucets. Appl. Environ. Microbiol. 501128–31
  10. Brenner DJ, Steigerwalt AG, McDade JE. 10.  1979. Classification of the Legionnaires' disease bacterium: Legionella pneumophila, genus novum, species nova, of the family Legionellaceae, familia nova. Ann. Intern. Med. 90656–58
  11. Burstein D, Amaro F, Zusman T, Lifshitz Z, Cohen O. 11.  et al. 2016. Genomic analysis of 38 Legionella species identifies large and diverse effector repertoires. Nat. Genet. 48167–75
  12. Burstein D, Zusman T, Degtyar E, Viner R, Segal G, Pupko T. 12.  2009. Genome-scale identification of Legionella pneumophila effectors using a machine learning approach. PLOS Pathog 5e1000508
  13. Byrd TF, Horwitz MA. 13.  1989. Interferon gamma-activated human monocytes downregulate transferrin receptors and inhibit the intracellular multiplication of Legionella pneumophila by limiting the availability of iron. J. Clin. Investig. 831457–65
  14. Carneiro LA, Travassos LH. 14.  2013. The interplay between NLRs and autophagy in immunity and inflammation. Front. Immunol. 4361
  15. Cazalet C, Rusniok C, Bruggemann H, Zidane N, Magnier A. 15.  et al. 2004. Evidence in the Legionella pneumophila genome for exploitation of host cell functions and high genome plasticity. Nat. Genet. 361165–73
  16. Chandler F, Blackmon J, Hicklin M, Cole R, Callaway C. 16.  1979. Ultrastructure of the agent of Legionnaires' disease in the human lung. Am. J. Clin. Pathol. 7143–50
  17. Chavrier P, Goud B. 17.  1999. The role of ARF and Rab GTPases in membrane transport. Curr. Opin. Cell Biol. 11466–75
  18. Chien M, Morozova I, Shi S, Sheng H, Chen J. 18.  et al. 2004. The genomic sequence of the accidental pathogen Legionella pneumophila. Science 3051966–68
  19. Choy A, Dancourt J, Mugo B, O'Connor TJ, Isberg RR. 19.  et al. 2012. The Legionella effector RavZ inhibits host autophagy through irreversible Atg8 deconjugation. Science 3381072–76
  20. Choy A, Roy CR. 20.  2013. Autophagy and bacterial infection: an evolving arms race. Trends Microbiol 21451–56
  21. Clemens DL, Lee BY, Horwitz MA. 21.  2000. Deviant expression of Rab5 on phagosomes containing the intracellular pathogens Mycobacterium tuberculosis and Legionella pneumophila is associated with altered phagosomal fate. Infect. Immun. 682671–84
  22. Cohen LB, Troemel ER. 22.  2015. Microbial pathogenesis and host defense in the nematode C. elegans. Curr.. Opin. Microbiol. 2394–101
  23. de Felipe KS, Glover RT, Charpentier X, Anderson OR, Reyes M. 23.  et al. 2008. Legionella eukaryotic-like type IV substrates interfere with organelle trafficking. PLOS Pathog 4e1000117
  24. de Felipe KS, Pampou S, Jovanovic OS, Pericone CD, Senna FY. 24.  et al. 2005. Evidence for acquisition of Legionella type IV secretion substrates via interdomain horizontal gene transfer. J. Bacteriol. 1877716–26
  25. Del Campo CM, Mishra AK, Wang Y-H, Roy CR, Janmey PA, Lambright DG. 25.  2014. Structural basis for PI (4) P-specific membrane recruitment of the Legionella pneumophila effector DrrA/SidM. Structure 22397–408
  26. Dengjel J, Schoor O, Fischer R, Reich M, Kraus M. 26.  et al. 2005. Autophagy promotes MHC class II presentation of peptides from intracellular source proteins. PNAS 1027922–27
  27. Deretic V. 27.  2005. Autophagy in innate and adaptive immunity. Trends Immunol 26523–28
  28. Derre I, Isberg RR. 28.  2004. Legionella pneumophila replication vacuole formation involves rapid recruitment of proteins of the early secretory system. Infect. Immun. 723048–53
  29. Diederen BM. 29.  2008. Legionella spp. and Legionnaires' disease. J. Infect. 561–12
  30. Dooley HC, Razi M, Polson HE, Girardin SE, Wilson MI, Tooze SA. 30.  2014. WIPI2 links LC3 conjugation with PI3P, autophagosome formation, and pathogen clearance by recruiting Atg12-5-16L1. Mol. Cell 55238–52
  31. Dorer MS, Kirton D, Bader JS, Isberg RR. 31.  2006. RNA interference analysis of Legionella in Drosophila cells: exploitation of early secretory apparatus dynamics. PLOS Pathog 2e34
  32. Dubuisson JF, Swanson MS. 32.  2006. Mouse infection by Legionella, a model to analyze autophagy. Autophagy 2179–82
  33. Eskelinen EL, Reggiori F, Baba M, Kovacs AL, Seglen PO. 33.  2011. Seeing is believing: the impact of electron microscopy on autophagy research. Autophagy 7935–56
  34. Fields BS. 34.  1996. The molecular ecology of legionellae. Trends Microbiol 4286–90
  35. Fliermans CB, Cherry WB, Orrison LH, Smith SJ, Tison DL, Pope DH. 35.  1981. Ecological distribution of Legionella pneumophila. Appl. Environ. Microbiol. 419–16
  36. Fraser DW, Tsai TR, Orenstein W, Parkin WE, Beecham HJ. 36.  et al. 1977. Legionnaires' Disease. N. Engl. J. Med. 2971189–97
  37. Ganley IG, Lam DH, Wang J, Ding X, Chen S, Jiang X. 37.  2009. ULK1·ATG13·FIP200 complex mediates mTOR signaling and is essential for autophagy. J. Biol. Chem. 28412297–305
  38. Gebran SJ, Yamamoto Y, Newton C, Klein TW, Friedman H. 38.  1994. Inhibition of Legionella pneumophila growth by gamma interferon in permissive A/J mouse macrophages: role of reactive oxygen species, nitric oxide, tryptophan, and iron(III). Infect. Immun. 623197–205
  39. Gomez-Valero L, Rusniok C, Rolando M, Neou M, Dervins-Ravault D. 39.  et al. 2014. Comparative analyses of Legionella species identifies genetic features of strains causing Legionnaires' disease. Genome Biol 15505
  40. Gutierrez MG, Master SS, Singh SB, Taylor GA, Colombo MI, Deretic V. 40.  2004. Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages. Cell 119753–66
  41. Haenssler E, Ramabhadran V, Murphy CS, Heidtman MI, Isberg RR. 41.  2015. Endoplasmic reticulum tubule protein reticulon 4 associates with the Legionella pneumophila vacuole and with translocated substrate Ceg9. Infect. Immun. 833479–89
  42. Hailey DW, Rambold AS, Satpute-Krishnan P, Mitra K, Sougrat R. 42.  et al. 2010. Mitochondria supply membranes for autophagosome biogenesis during starvation. Cell 141656–67
  43. Hamasaki M, Furuta N, Matsuda A, Nezu A, Yamamoto A. 43.  et al. 2013. Autophagosomes form at ER-mitochondria contact sites. Nature 495389–93
  44. Hemelaar J, Lelyveld VS, Kessler BM, Ploegh HL. 44.  2003. A single protease, Apg4B, is specific for the autophagy-related ubiquitin-like proteins GATE-16, MAP1-LC3, GABARAP, and Apg8L. J. Biol. Chem. 27851841–50
  45. Hoffmann C, Harrison CF, Hilbi H. 45.  2014. The natural alternative: Protozoa as cellular models for Legionella infection. Cell Microbiol 1615–26
  46. Horenkamp FA, Kauffman KJ, Kohler LJ, Sherwood RK, Krueger KP. 46.  et al. 2015. The Legionella anti-autophagy effector RavZ targets the autophagosome via PI3P- and curvature-sensing motifs. Dev. Cell 34569–76
  47. Horwitz MA. 47.  1983. Formation of a novel phagosome by the Legionnaires' disease bacterium (Legionella pneumophila) in human monocytes. J. Exp. Med. 1581319–31
  48. Horwitz MA. 48.  1987. Characterization of avirulent mutant Legionella pneumophila that survive but do not multiply within human monocytes. J. Exp. Med. 1661310–28
  49. Horwitz MA, Maxfield FR. 49.  1984. Legionella pneumophila inhibits acidification of its phagosome in human monocytes. J. Cell Biol. 991936–43
  50. Horwitz MA, Silverstein SC. 50.  1980. Legionnaires' disease bacterium (Legionella pneumophila) multiples intracellularly in human monocytes. J. Clin. Investig. 66441–50
  51. Hsu F, Zhu W, Brennan L, Tao L, Luo Z-Q, Mao Y. 51.  2012. Structural basis for substrate recognition by a unique Legionella phosphoinositide phosphatase. PNAS 10913567–72
  52. Huang J, Canadien V, Lam GY, Steinberg BE, Dinauer MC. 52.  et al. 2009. Activation of antibacterial autophagy by NADPH oxidases. PNAS 1066226–31
  53. Hubber A, Arasaki K, Nakatsu F, Hardiman C, Lambright D. 53.  et al. 2014. The machinery at endoplasmic reticulum-plasma membrane contact sites contributes to spatial regulation of multiple Legionella effector proteins. PLOS Pathog 10e1004222
  54. Ichimura Y, Imamura Y, Emoto K, Umeda M, Noda T, Ohsumi Y. 54.  2004. In vivo and in vitro reconstitution of Atg8 conjugation essential for autophagy. J. Biol. Chem. 27940584–92
  55. Ichimura Y, Kirisako T, Takao T, Satomi Y, Shimonishi Y. 55.  et al. 2000. A ubiquitin-like system mediates protein lipidation. Nature 408488–92
  56. Itakura E, Kishi C, Inoue K, Mizushima N. 56.  2008. Beclin 1 forms two distinct phosphatidylinositol 3-kinase complexes with mammalian Atg14 and UVRAG. Mol. Biol. Cell 195360–72
  57. Jabir MS, Ritchie ND, Li D, Bayes HK, Tourlomousis P. 57.  et al. 2014. Caspase-1 cleavage of the TLR adaptor TRIF inhibits autophagy and beta-interferon production during Pseudomonas aeruginosa infection. Cell Host Microbe 15214–27
  58. Janeway CA Jr. 58.  1989. Approaching the asymptote? Evolution and revolution in immunology. Cold Spring Harb. Symp. Quant. Biol. 54(Part 11–13
  59. Joshi AD, Sturgill-Koszycki S, Swanson MS. 59.  2001. Evidence that Dot-dependent and -independent factors isolate the Legionella pneumophila phagosome from the endocytic network in mouse macrophages. Cell. Microbiol. 399–114
  60. Jung CH, Jun CB, Ro SH, Kim YM, Otto NM. 60.  et al. 2009. ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. Mol. Biol. Cell 201992–2003
  61. Kabeya Y, Mizushima N, Ueno T, Yamamoto A, Kirisako T. 61.  et al. 2000. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J 195720–28
  62. Kagan JC, Roy CR. 62.  2002. Legionella phagosomes intercept vesicular traffic from endoplasmic reticulum exit sites. Nat. Cell Biol. 4945–54
  63. Kagan JC, Stein MP, Pypaert M, Roy CR. 63.  2004. Legionella subvert the functions of Rab1 and Sec22b to create a replicative organelle. J. Exp. Med. 1991201–11
  64. Kageyama S, Omori H, Saitoh T, Sone T, Guan JL. 64.  et al. 2011. The LC3 recruitment mechanism is separate from Atg9L1-dependent membrane formation in the autophagic response against Salmonella. Mol. Biol. Cell 222290–300
  65. Kihara A, Noda T, Ishihara N, Ohsumi Y. 65.  2001. Two distinct Vps34 phosphatidylinositol 3-kinase complexes function in autophagy and carboxypeptidase Y sorting in Saccharomyces cerevisiae. J. Cell Biol. 152519–30
  66. Kirisako T, Ichimura Y, Okada H, Kabeya Y, Mizushima N. 66.  et al. 2000. The reversible modification regulates the membrane-binding state of Apg8/Aut7 essential for autophagy and the cytoplasm to vacuole targeting pathway. J. Cell Biol. 151263–76
  67. Kraft C, Kijanska M, Kalie E, Siergiejuk E, Lee SS. 67.  et al. 2012. Binding of the Atg1/ULK1 kinase to the ubiquitin-like protein Atg8 regulates autophagy. EMBO J 313691–703
  68. Kraft C, Peter M, Hofmann K. 68.  2010. Selective autophagy: ubiquitin-mediated recognition and beyond. Nat. Cell Biol. 12836–41
  69. Ku B, Woo JS, Liang C, Lee KH, Hong HS. 69.  et al. 2008. Structural and biochemical bases for the inhibition of autophagy and apoptosis by viral BCL-2 of murine gamma-herpesvirus 68. PLOS Pathog 4e25
  70. Liang XH, Jackson S, Seaman M, Brown K, Kempkes B. 70.  et al. 1999. Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature 402672–6
  71. Maiuri MC, Criollo A, Tasdemir E, Vicencio JM, Tajeddine N. 71.  et al. 2007. BH3-only proteins and BH3 mimetics induce autophagy by competitively disrupting the interaction between Beclin 1 and Bcl-2/Bcl-XL. Autophagy 3374–76
  72. Maiuri MC, Le Toumelin G, Criollo A, Rain JC, Gautier F. 72.  et al. 2007. Functional and physical interaction between Bcl-XL and a BH3-like domain in Beclin-1. EMBO J 262527–39
  73. Marra A, Blander SJ, Horwitz MA, Shuman HA. 73.  1992. Identification of a Legionella pneumophila locus required for intracellular multiplication in human macrophages. PNAS 899607–11
  74. Marston BJ, Plouffe JF, File TM Jr., Hackman BA, Salstrom SJ. 74.  et al. 1997. Incidence of community-acquired pneumonia requiring hospitalization: results of a population-based active surveillance study in Ohio. Arch. Intern. Med. 1571709–18
  75. Martinez J, Almendinger J, Oberst A, Ness R, Dillon CP. 75.  et al. 2011. Microtubule-associated protein 1 light chain 3 alpha (LC3)-associated phagocytosis is required for the efficient clearance of dead cells. PNAS 10817396–401
  76. Martinez J, Malireddi RKS, Lu Q, Cunha LD, Pelletier S. 76.  et al. 2015. Molecular characterization of LC3-associated phagocytosis reveals distinct roles for Rubicon, NOX2 and autophagy proteins. Nat. Cell Biol. 17893–906
  77. Matsuda F, Fujii J, Yoshida S. 77.  2009. Autophagy induced by 2-deoxy-d-glucose suppresses intracellular multiplication of Legionella pneumophila in A/J mouse macrophages. Autophagy 5484–93
  78. Matsunaga K, Klein TW, Friedman H, Yamamoto Y. 78.  2001. Involvement of nicotinic acetylcholine receptors in suppression of antimicrobial activity and cytokine responses of alveolar macrophages to Legionella pneumophila infection by nicotine. J. Immunol. 1676518–24
  79. Matsunaga K, Saitoh T, Tabata K, Omori H, Satoh T. 79.  et al. 2009. Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally regulate autophagy at different stages. Nat. Cell Biol. 11385–96
  80. Mizushima N, Yoshimori T, Ohsumi Y. 80.  2011. The role of Atg proteins in autophagosome formation. Annu. Rev. Cell Dev. Biol. 27107–32
  81. Muder RR, Yu VL. 81.  2002. Infection due to Legionella species other than L. pneumophila. Clin. Infect. Dis. 35990–98
  82. Mukherjee S, Liu X, Arasaki K, McDonough J, Galan JE, Roy CR. 82.  2011. Modulation of Rab GTPase function by a protein phosphocholine transferase. Nature 477103–6
  83. Müller MP, Peters H, Blümer J, Blankenfeldt W, Goody RS, Itzen A. 83.  2010. The Legionella effector protein DrrA AMPylates the membrane traffic regulator Rab1b. Science 329946–49
  84. Murata T, Delprato A, Ingmundson A, Toomre DK, Lambright DG, Roy CR. 84.  2006. The Legionella pneumophila effector protein DrrA is a Rab1 guanine nucleotide-exchange factor. Nat. Cell Biol. 8971–77
  85. Nagai H, Cambronne ED, Kagan JC, Amor JC, Kahn RA, Roy CR. 85.  2005. A C-terminal translocation signal required for Dot/Icm-dependent delivery of the Legionella RalF protein to host cells. PNAS 102826–31
  86. Nagai H, Kagan JC, Zhu X, Kahn RA, Roy CR. 86.  2002. A bacterial guanine nucleotide exchange factor activates ARF on Legionella phagosomes. Science 295679–82
  87. Nagai H, Roy CR. 87.  2001. The DotA protein from Legionella pneumophila is secreted by a novel process that requires the Dot/Icm transporter. EMBO J 205962–70
  88. Nakagawa I, Amano A, Mizushima N, Yamamoto A, Yamaguchi H. 88.  et al. 2004. Autophagy defends cells against invading group A Streptococcus. Science 3061037–40
  89. Nash TW, Libby DM, Horwitz MA. 89.  1988. IFN-gamma-activated human alveolar macrophages inhibit the intracellular multiplication of Legionella pneumophila. J. Immunol. 1403978–81
  90. Neunuebel MR, Chen Y, Gaspar AH, Backlund PS Jr., Yergey A, Machner MP. 90.  2011. De-AMPylation of the small GTPase Rab1 by the pathogen Legionella pneumophila. Science 333453–56
  91. Neunuebel MR, Mohammadi S, Jarnik M, Machner MP. 91.  2012. Legionella pneumophila LidA affects nucleotide binding and activity of the host GTPase Rab1. J. Bacteriol. 1941389–400
  92. O'Connor TJ, Adepoju Y, Boyd D, Isberg RR. 92.  2011. Minimization of the Legionella pneumophila genome reveals chromosomal regions involved in host range expansion. PNAS 108:14733–40 [Google Scholar]
  93. O'Connor TJ, Boyd D, Dorer MS, Isberg RR. 93.  2012. Aggravating genetic interactions allow a solution to redundancy in a bacterial pathogen. Science 3381440–44
  94. Ogawa M, Yoshimori T, Suzuki T, Sagara H, Mizushima N, Sasakawa C. 94.  2005. Escape of intracellular Shigella from autophagy. Science 307727–31
  95. Ogretmen B, Hannun YA. 95.  2004. Biologically active sphingolipids in cancer pathogenesis and treatment. Nat. Rev. Cancer 4604–16
  96. O'Loughlin RE, Kightlinger L, Werpy MC, Brown E, Stevens V. 96.  et al. 2007. Restaurant outbreak of Legionnaires' disease associated with a decorative fountain: an environmental and case-control study. BMC Infect. Dis. 793
  97. Oskouian B, Sooriyakumaran P, Borowsky AD, Crans A, Dillard-Telm L. 97.  et al. 2006. Sphingosine-1-phosphate lyase potentiates apoptosis via p53- and p38-dependent pathways and is down-regulated in colon cancer. PNAS 103:17384–89 [Google Scholar]
  98. Paludan C, Schmid D, Landthaler M, Vockerodt M, Kube D. 98.  et al. 2005. Endogenous MHC class II processing of a viral nuclear antigen after autophagy. Science 307593–96
  99. Pattingre S, Tassa A, Qu X, Garuti R, Liang XH. 99.  et al. 2005. Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell 122:927–39 [Google Scholar]
  100. Pereira-Leal JB, Seabra MC. 100.  2000. The mammalian Rab family of small GTPases: Definition of family and subfamily sequence motifs suggests a mechanism for functional specificity in the Ras superfamily. J. Mol. Biol. 3011077–87
  101. Polson HE, de Lartigue J, Rigden DJ, Reedijk M, Urbe S. 101.  et al. 2010. Mammalian Atg18 (WIPI2) localizes to omegasome-anchored phagophores and positively regulates LC3 lipidation. Autophagy 6506–22
  102. Reinisch KM, De Camilli P. 102.  2016. SMP-domain proteins at membrane contact sites: structure and function. Biochim. Biophys. Acta. 18618 Part B924–27
  103. Robinson CG, Roy CR. 103.  2006. Attachment and fusion of endoplasmic reticulum with vacuoles containing Legionella pneumophila. Cell Microbiol 8793–805
  104. Rolando M, Escoll P, Nora T, Botti J, Boitez V. 104.  et al. 2016. Legionella pneumophila S1P-lyase targets host sphingolipid metabolism and restrains autophagy. PNAS 113:1901 [Google Scholar]
  105. Roy CR, Berger KH, Isberg RR. 105.  1998. Legionella pneumophila DotA protein is required for early phagosome trafficking decisions that occur within minutes of bacterial uptake. Mol. Microbiol. 28:663–74 [Google Scholar]
  106. Sanjuan MA, Dillon CP, Tait SW, Moshiach S, Dorsey F. 106.  et al. 2007. Toll-like receptor signalling in macrophages links the autophagy pathway to phagocytosis. Nature 4501253–57
  107. Scherz-Shouval R, Sagiv Y, Shorer H, Elazar Z. 107.  2003. The COOH terminus of GATE-16, an intra-Golgi transport modulator, is cleaved by the human cysteine protease HsApg4A. J. Biol. Chem. 27814053–58
  108. Schoebel S, Cichy AL, Goody RS, Itzen A. 108.  2011. Protein LidA from Legionella is a Rab GTPase supereffector. PNAS 108:17945–50 [Google Scholar]
  109. Schwab SR, Pereira JP, Matloubian M, Xu Y, Huang Y, Cyster JG. 109.  2005. Lymphocyte sequestration through S1P lyase inhibition and disruption of S1P gradients. Science 3091735–39
  110. Segal G, Purcell M, Shuman HA. 110.  1998. Host cell killing and bacterial conjugation require overlapping sets of genes within a 22-kb region of the Legionella pneumophila genome. PNAS 951669–74
  111. Segal G, Russo JJ, Shuman HA. 111.  1999. Relationships between a new type IV secretion system and the icm/dot virulence system of Legionella pneumophila. Mol. Microbiol. 34799–809
  112. Shen LN, Liu H, Dong C, Xirodimas D, Naismith JH, Hay RT. 112.  2005. Structural basis of NEDD8 ubiquitin discrimination by the deNEDDylating enzyme NEDP1. EMBO J 241341–51
  113. Sherwood RK, Roy CR. 113.  2013. A Rab-centric perspective of bacterial pathogen-occupied vacuoles. Cell Host Microbe 14:256–68 [Google Scholar]
  114. Shi CS, Kehrl JH. 114.  2008. MyD88 and Trif target Beclin 1 to trigger autophagy in macrophages. J. Biol. Chem. 28333175–82
  115. Shin S. 115.  2012. Innate immunity to intracellular pathogens: lessons learned from Legionella pneumophila. Adv. Appl. Microbiol. 7943–71
  116. Sporri R, Joller N, Hilbi H, Oxenius A. 116.  2008. A novel role for neutrophils as critical activators of NK cells. J. Immunol. 181:7121–30 [Google Scholar]
  117. Steinert M, Ott M, Lück PC, Tannich E, Hacker J. 117.  1994. Studies on the uptake and intracellular replication of Legionella pneumophila in protozoa and in macrophage-like cells. FEMS Microbiol. Ecol. 15299–307
  118. Sturgill-Koszycki S, Swanson MS. 118.  2000. Legionella pneumophila replication vacuoles mature into acidic, endocytic organelles. J. Exp. Med. 192:1261–72 [Google Scholar]
  119. Sugawara K, Suzuki NN, Fujioka Y, Mizushima N, Ohsumi Y, Inagaki F. 119.  2004. The crystal structure of microtubule-associated protein light chain 3, a mammalian homologue of Saccharomyces cerevisiae Atg8. Genes to Cells 9611–18
  120. Sugawara K, Suzuki NN, Fujioka Y, Mizushima N, Ohsumi Y, Inagaki F. 120.  2005. Structural basis for the specificity and catalysis of human Atg4B responsible for mammalian autophagy. J. Biol. Chem. 28040058–65
  121. Swanson MS, Isberg RR. 121.  1995. Association of Legionella pneumophila with the macrophage endoplasmic reticulum. Infect. Immun. 633609–20
  122. Takegawa K, DeWald DB, Emr SD. 122.  1995. Schizosaccharomyces pombe Vps34p, a phosphatidylinositol-specific PI 3-kinase essential for normal cell growth and vacuole morphology. J. Cell Sci. 108Part 123745–56
  123. Tan Y, Arnold RJ, Luo ZQ. 123.  2011. Legionella pneumophila regulates the small GTPase Rab1 activity by reversible phosphorylcholination. PNAS 108:21212–17 [Google Scholar]
  124. Tan Y, Luo ZQ. 124.  2011. Legionella pneumophila SidD is a deAMPylase that modifies Rab1. Nature 475506–9
  125. Tateda K, Moore TA, Deng JC, Newstead MW, Zeng X. 125.  et al. 2001. Early recruitment of neutrophils determines subsequent T1/T2 host responses in a murine model of Legionella pneumophila pneumonia. J. Immunol. 166:3355–61 [Google Scholar]
  126. Tateda K, Moore TA, Newstead MW, Tsai WC, Zeng X. 126.  et al. 2001. Chemokine-dependent neutrophil recruitment in a murine model of Legionella pneumonia: potential role of neutrophils as immunoregulatory cells. Infect. Immun. 692017–24
  127. Thurston TL, Ryzhakov G, Bloor S, von Muhlinen N, Randow F. 127.  2009. The TBK1 adaptor and autophagy receptor NDP52 restricts the proliferation of ubiquitin-coated bacteria. Nat. Immunol. 10:1215–21 [Google Scholar]
  128. Thurston TL, Wandel MP, von Muhlinen N, Foeglein A, Randow F. 128.  2012. Galectin 8 targets damaged vesicles for autophagy to defend cells against bacterial invasion. Nature 482414–18
  129. Tilney LG, Harb OS, Connelly PS, Robinson CG, Roy CR. 129.  2001. How the parasitic bacterium Legionella pneumophila modifies its phagosome and transforms it into rough ER: implications for conversion of plasma membrane to the ER membrane. J. Cell Sci. 1144637–50
  130. Travassos LH, Carneiro LA, Ramjeet M, Hussey S, Kim YG. 130.  et al. 2010. Nod1 and Nod2 direct autophagy by recruiting ATG16L1 to the plasma membrane at the site of bacterial entry. Nat. Immunol. 1155–62
  131. Tumbarello DA, Manna PT, Allen M, Bycroft M, Arden SD. 131.  et al. 2015. The autophagy receptor TAX1BP1 and the molecular motor myosin VI are required for clearance of Salmonella Typhimurium by autophagy. PLOS Pathog 11e1005174 Correction. 2016. PLOS Pathog. doi:10.1371/journal.ppat.1005433
  132. Van Veldhoven PP, Gijsbers S, Mannaerts GP, Vermeesch JR, Brys V. 132.  2000. Human sphingosine-1-phosphate lyase: cDNA cloning, functional expression studies and mapping to chromosome 10q22(1). Biochim. Biophys. Acta 1487128–34
  133. Vance RE. 133.  2010. Immunology taught by bacteria. J. Clin. Immunol. 30507–11
  134. Vance RE, Isberg RR, Portnoy DA. 134.  2009. Patterns of pathogenesis: discrimination of pathogenic and nonpathogenic microbes by the innate immune system. Cell Host Microbe 610–21
  135. Vincent CD, Friedman JR, Jeong KC, Buford EC, Miller JL, Vogel JP. 135.  2006. Identification of the core transmembrane complex of the Legionella Dot/Icm type IV secretion system. Mol. Microbiol. 621278–91
  136. Vogel JP, Andrews HL, Wong SK, Isberg RR. 136.  1998. Conjugative transfer by the virulence system of Legionella pneumophila. Science 279873–76
  137. Vural A, Kehrl JH. 137.  2014. Autophagy in macrophages: Impacting inflammation and bacterial infection. Scientifica 2014825463
  138. Weber SS, Ragaz C, Reus K, Nyfeler Y, Hilbi H. 138.  2006. Legionella pneumophila exploits PI (4) P to anchor secreted effector proteins to the replicative vacuole. PLOS Pathog 2e46
  139. Wild P, Farhan H, McEwan DG, Wagner S, Rogov VV. 139.  et al. 2011. Phosphorylation of the autophagy receptor optineurin restricts Salmonella growth. Science 333228–33
  140. Xia P, Wadham C. 140.  2011. Sphingosine 1-phosphate, a key mediator of the cytokine network: juxtacrine signaling. Cytokine Growth Factor Rev 2245–53
  141. Xu Y, Fattah EA, Liu XD, Jagannath C, Eissa NT. 141.  2013. Harnessing of TLR-mediated autophagy to combat mycobacteria in macrophages. Tuberculosis 93Suppl.S33–37
  142. Xu Y, Jagannath C, Liu XD, Sharafkhaneh A, Kolodziejska KE, Eissa NT. 142.  2007. Toll-like receptor 4 is a sensor for autophagy associated with innate immunity. Immunity 27135–44
  143. Yorimitsu T, Nair U, Yang Z, Klionsky DJ. 143.  2006. Endoplasmic reticulum stress triggers autophagy. J. Biol. Chem. 28130299–304
  144. Yu VL, Plouffe JF, Pastoris MC, Stout JE, Schousboe M. 144.  et al. 2002. Distribution of Legionella species and serogroups isolated by culture in patients with sporadic community-acquired legionellosis: an international collaborative survey. J. Infect. Dis. 186127–28
  145. Zamboni DS, Kobayashi KS, Kohlsdorf T, Ogura Y, Long EM. 145.  et al. 2006. The Birc1e cytosolic pattern-recognition receptor contributes to the detection and control of Legionella pneumophila infection. Nat. Immunol. 7318–25
  146. Zhong Y, Wang QJ, Li X, Yan Y, Backer JM. 146.  et al. 2009. Distinct regulation of autophagic activity by Atg14L and Rubicon associated with Beclin 1-phosphatidylinositol-3-kinase complex. Nat. Cell Biol. 11468–76
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