Identification of Two Legionella pneumophila Effectors that Manipulate Host Phospholipids Biosynthesis

PLoS Pathogens

Volumn 8, Issue 11, 2012, Pages

  Viner, Ram ^a   Chetrit, David ^a   Ehrlich, Marcelo ^a   Segal, Gil ^a  

^a TEL AVIV UNIVERSITY   (Israel)

Author keywords

[No Author keywords available]

Indexed keywords

DIACYLGLYCEROL KINASE; PHOSPHATIDATE PHOSPHATASE;

ANIMAL CELL; ARTICLE; CANDIDA ALBICANS; CLONING; CONFOCAL MICROSCOPY; CONTROLLED STUDY; FLUORESCENCE ANALYSIS; GENE DELETION; GENETIC ANALYSIS; HUMAN; HUMAN CELL; LEGIONELLA PNEUMOPHILA; LETHALITY; NONHUMAN; PHOSPHOLIPID SYNTHESIS; PLASMID; POINT MUTATION; POLYACRYLAMIDE GEL ELECTROPHORESIS; POLYMERASE CHAIN REACTION; SACCHAROMYCES CEREVISIAE; SITE DIRECTED MUTAGENESIS; TETRAHYMENA THERMOPHILA; WESTERN BLOTTING;

BACTERIAL OUTER MEMBRANE PROTEINS; BACTERIAL SECRETION SYSTEMS; HL-60 CELLS; HUMANS; LEGIONELLA PNEUMOPHILA; LEGIONNAIRES' DISEASE; MACROPHAGES; MEMBRANE PROTEINS; NUCLEAR PROTEINS; PHAGOSOMES; PHOSPHATIDATE PHOSPHATASE; PHOSPHOLIPIDS; REPRESSOR PROTEINS; SACCHAROMYCES CEREVISIAE; SACCHAROMYCES CEREVISIAE PROTEINS;

BACTERIA (MICROORGANISMS); LEGIONELLA PNEUMOPHILA; MAMMALIA;

EID: 84870789375     PISSN: 15537366     EISSN: 15537374     Source Type: Journal    
DOI: 10.1371/journal.ppat.1002988     Document Type: Article

References (107)

1. Fields BS, (1996) The molecular ecology of Legionellae. Trends Microbiol 4: 286-290.
2. Horwitz MA, (1983) Formation of a novel phagosome by the Legionnaires' disease bacterium (Legionella pneumophila) in human monocytes. J Exp Med 158: 1319-1331.
3. Tilney LG, Harb OS, Connelly PS, Robinson CG, Roy CR, (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 114: 4637-4650.
4. Horwitz MA, (1983) The Legionnaires' disease bacterium (Legionella pneumophila) inhibits phagosome-lysosome fusion in human monocytes. J Exp Med 158: 2108-2126.
5. Horwitz MA, Silverstein SC, (1980) Legionnaires' disease bacterium (Legionella pneumophila) multiplies intracellularly in human monocytes. J Clin Invest 60: 441-450.
6. Gomez-Valero L, Rusniok C, Cazalet C, Buchrieser C, (2011) Comparative and functional genomics of legionella identified eukaryotic like proteins as key players in host-pathogen interactions. Front Microbiol 2: 208.
7. Hubber A, Roy CR, (2010) Modulation of host cell function by Legionella pneumophila type IV effectors. Annu Rev Cell Dev Biol 26: 261-283.
8. Beare PA, Gilk SD, Larson CL, Hill J, Stead CM, et al. (2011) Dot/Icm type IVB secretion system requirements for Coxiella burnetii growth in human macrophages. MBio 2: e00175-00111.
9. Segal G, Feldman M, Zusman T, (2005) The Icm/Dot type-IV secretion systems of Legionella pneumophila and Coxiella burnetii. FEMS Microbiol Rev 29: 65-81.
10. Zamboni DS, McGrath S, Rabinovitch M, Roy CR, (2003) Coxiella burnetii express type IV secretion system proteins that function similarly to components of the Legionella pneumophila Dot/Icm system. Mol Microbiol 49: 965-976.
11. Zusman T, Yerushalmi G, Segal G, (2003) Functional similarities between the icm/dot pathogenesis systems of Coxiella burnetii and Legionella pneumophila. Infect Immun 71: 3714-3723.
12. Ghigo E, Pretat L, Desnues B, Capo C, Raoult D, et al. (2009) Intracellular life of Coxiella burnetii in macrophages. Ann N Y Acad Sci 1166: 55-66.
13. Ninio S, Roy CR, (2007) Effector proteins translocated by Legionella pneumophila: strength in numbers. Trends Microbiol 15: 372-380.
14. Burstein D, Zusman T, Degtyar E, Viner R, Segal G, et al. (2009) Genome-scale identification of Legionella pneumophila effectors using a machine learning approach. PLoS Pathog 5: e1000508.
15. Heidtman M, Chen EJ, Moy MY, Isberg RR, (2009) Large-scale identification of Legionella pneumophila Dot/Icm substrates that modulate host cell vesicle trafficking pathways. Cell Microbiol 11: 230-248.
16. Huang L, Boyd D, Amyot WM, Hempstead AD, Luo ZQ, et al. (2011) The E Block motif is associated with Legionella pneumophila translocated substrates. Cell Microbiol 13: 227-245.
17. Kubori T, Hyakutake A, Nagai H, (2008) Legionella translocates an E3 ubiquitin ligase that has multiple U-boxes with distinct functions. Mol Microbiol 67: 1307-1319.
18. Luo ZQ, Isberg RR, (2004) Multiple substrates of the Legionella pneumophila Dot/Icm system identified by interbacterial protein transfer. Proc Natl Acad Sci USA 101: 841-846.
19. Zhu W, Banga S, Tan Y, Zheng C, Stephenson R, et al. (2011) Comprehensive identification of protein substrates of the Dot/Icm type IV transporter of Legionella pneumophila. PLoS One 6: e17638.
20. Ge J, Shao F, (2011) Manipulation of host vesicular trafficking and innate immune defence by Legionella Dot/Icm effectors. Cell Microbiol 13: 1870-1880.
21. Machner MP, Isberg RR, (2007) A bifunctional bacterial protein links GDI displacement to Rab1 activation. Science 318: 974-977.
22. Ingmundson A, Delprato A, Lambright DG, Roy CR, (2007) Legionella pneumophila proteins that regulate Rab1 membrane cycling. Nature 450: 365-369.
23. Muller MP, Peters H, Blumer J, Blankenfeldt W, Goody RS, et al. (2010) The Legionella effector protein DrrA AMPylates the membrane traffic regulator Rab1b. Science 329: 946-949.
24. Tan Y, Luo ZQ, (2011) Legionella pneumophila SidD is a deAMPylase that modifies Rab1. Nature 475: 506-509.
25. Mukherjee S, Liu X, Arasaki K, McDonough J, Galan JE, et al. (2011) Modulation of Rab GTPase function by a protein phosphocholine transferase. Nature 477: 103-106.
26. Goody PR, Heller K, Oesterlin LK, Muller MP, Itzen A, et al. (2012) Reversible phosphocholination of Rab proteins by Legionella pneumophila effector proteins. EMBO J 31: 1774-84.
27. Tan Y, Arnold RJ, Luo ZQ, (2011) Legionella pneumophila regulates the small GTPase Rab1 activity by reversible phosphorylcholination. Proc Natl Acad Sci USA 108: 21212-21217.
28. Cheng W, Yin K, Lu D, Li B, Zhu D, et al. (2012) Structural Insights into a Unique Legionella pneumophila Effector LidA Recognizing Both GDP and GTP Bound Rab1 in Their Active State. PLoS Pathog 8: e1002528.
29. Neunuebel MR, Mohammadi S, Jarnik M, Machner MP, (2012) Legionella pneumophila LidA Affects Nucleotide Binding and Activity of the Host GTPase Rab1. J Bacteriol 194: 1389-1400.
30. Machner MP, Isberg RR, (2006) Targeting of host rab GTPase function by the intravacuolar pathogen Legionella pneumophila. Dev Cell 11: 47-56.
31. Kubori T, Shinzawa N, Kanuka H, Nagai H, (2010) Legionella metaeffector exploits host proteasome to temporally regulate cognate effector. PLoS Pathog 6: e1001216.
32. Al-Khodor S, Price CT, Habyarimana F, Kalia A, Abu Kwaik Y, (2008) A Dot/Icm-translocated ankyrin protein of Legionella pneumophila is required for intracellular proliferation within human macrophages and protozoa. Mol Microbiol 70: 908-923.
33. Lomma M, Dervins-Ravault D, Rolando M, Nora T, Newton HJ, et al. (2010) The Legionella pneumophila F-box protein Lpp2082 (AnkB) modulates ubiquitination of the host protein parvin B and promotes intracellular replication. Cell Microbiol 12: 1272-1291.
34. Price CT, Al-Khodor S, Al-Quadan T, Abu Kwaik Y, (2010) Indispensable role for the eukaryotic-like ankyrin domains of the ankyrin B effector of Legionella pneumophila within macrophages and amoebae. Infect Immun 78: 2079-2088.
35. Price CT, Al-Quadan T, Santic M, Jones SC, Abu Kwaik Y, (2010) Exploitation of conserved eukaryotic host cell farnesylation machinery by an F-box effector of Legionella pneumophila. J Exp Med 207: 1713-1726.
36. Price CT, Al-Quadan T, Santic M, Rosenshine I, Abu Kwaik Y, (2011) Host proteasomal degradation generates amino acids essential for intracellular bacterial growth. Science 334: 1553-1557.
37. Ensminger AW, Isberg RR, (2010) E3 ubiquitin ligase activity and targeting of BAT3 by multiple Legionella pneumophila translocated substrates. Infect Immun 78: 3905-3919.
38. Belyi Y, Jank T, Aktories K, (2011) Effector glycosyltransferases in legionella. Front Microbiol 2: 76.
39. Hurtado-Guerrero R, Zusman T, Pathak S, Ibrahim AF, Shepherd S, et al. (2010) Molecular mechanism of elongation factor 1A inhibition by a Legionella pneumophila glycosyltransferase. Biochem J 426: 281-292.
40. Shen X, Banga S, Liu Y, Xu L, Gao P, et al. (2009) Targeting eEF1A by a Legionella pneumophila effector leads to inhibition of protein synthesis and induction of host stress response. Cell Microbiol 11: 911-926.
41. Ge J, Xu H, Li T, Zhou Y, Zhang Z, et al. (2009) A Legionella type IV effector activates the NF-kappaB pathway by phosphorylating the IkappaB family of inhibitors. Proc Natl Acad Sci USA 106: 13725-13730.
42. Losick VP, Haenssler E, Moy MY, Isberg RR, (2010) LnaB: a Legionella pneumophila activator of NF-kappaB. Cell Microbiol 12: 1083-1097.
43. Shohdy N, Efe JA, Emr SD, Shuman HA, (2005) Pathogen effector protein screening in yeast identifies Legionella factors that interfere with membrane trafficking. Proc Natl Acad Sci USA 102: 4866-4871.
44. VanRheenen SM, Luo ZQ, O'Connor T, Isberg RR, (2006) Members of a Legionella pneumophila family of proteins with ExoU (phospholipase A) active sites are translocated to target cells. Infect Immun 74: 3597-3606.
45. Lang C, Flieger A, (2011) Characterisation of Legionella pneumophila phospholipases and their impact on host cells. Eur J Cell Biol 90: 903-912.
46. Degtyar E, Zusman T, Ehrlich M, Segal G, (2009) A Legionella effector acquired from protozoa is involved in sphingolipids metabolism and is targeted to the host cell mitochondria. Cell Microbiol 11: 1219-1135.
47. Brombacher E, Urwyler S, Ragaz C, Weber SS, Kami K, et al. (2009) Rab1 guanine nucleotide exchange factor SidM is a major phosphatidylinositol 4-phosphate-binding effector protein of Legionella pneumophila. J Biol Chem 284: 4846-4856.
48. Weber SS, Ragaz C, Reus K, Nyfeler Y, Hilbi H, (2006) Legionella pneumophila exploits PI(4)P to anchor secreted effector proteins to the replicative vacuole. PLoS Pathog 2: e46.
49. Jank T, Bohmer KE, Tzivelekidis T, Schwan C, Belyi Y, et al. (2012) Domain organization of Legionella effector SetA. Cell Microbiol 14: 852-68.
50. Weber SS, Ragaz C, Hilbi H, (2009) The inositol polyphosphate 5-phosphatase OCRL1 restricts intracellular growth of Legionella, localizes to the replicative vacuole and binds to the bacterial effector LpnE. Cell Microbiol 11: 442-460.
51. Lossi NS, Rolhion N, Magee AI, Boyle C, Holden DW, (2008) The Salmonella SPI-2 effector SseJ exhibits eukaryotic activator-dependent phospholipase A and glycerophospholipid: cholesterol acyltransferase activity. Microbiology 154: 2680-2688.
52. Nawabi P, Catron DM, Haldar K, (2008) Esterification of cholesterol by a type III secretion effector during intracellular Salmonella infection. Mol Microbiol 68: 173-185.
53. Hernandez LD, Hueffer K, Wenk MR, Galan JE, (2004) Salmonella modulates vesicular traffic by altering phosphoinositide metabolism. Science 304: 1805-1807.
54. Mallo GV, Espina M, Smith AC, Terebiznik MR, Aleman A, et al. (2008) SopB promotes phosphatidylinositol 3-phosphate formation on Salmonella vacuoles by recruiting Rab5 and Vps34. J Cell Biol 182: 741-752.
55. Terebiznik MR, Vieira OV, Marcus SL, Slade A, Yip CM, et al. (2002) Elimination of host cell PtdIns(4,5)P(2) by bacterial SigD promotes membrane fission during invasion by Salmonella. Nat Cell Biol 4: 766-773.
56. Clemens DL, Horwitz MA, (1995) Characterization of the Mycobacterium tuberculosis phagosome and evidence that phagosomal maturation is inhibited. J Exp Med 181: 257-270.
57. Vergne I, Chua J, Lee HH, Lucas M, Belisle J, et al. (2005) Mechanism of phagolysosome biogenesis block by viable Mycobacterium tuberculosis. Proc Natl Acad Sci USA 102: 4033-4038.
58. Carey KL, Newton HJ, Luhrmann A, Roy CR, (2011) The Coxiella burnetii Dot/Icm system delivers a unique repertoire of type IV effectors into host cells and is required for intracellular replication. PLoS Pathog 7: e1002056.
59. Chen C, Banga S, Mertens K, Weber MM, Gorbaslieva I, et al. (2010) Large-scale identification and translocation of type IV secretion substrates by Coxiella burnetii. Proc Natl Acad Sci USA 107: 21755-21760.
60. Newton HJ, Roy CR, (2011) The Coxiella burnetii Dot/Icm system creates a comfortable home through lysosomal renovation. MBio 2: e00226-00211.
61. Pan X, Luhrmann A, Satoh A, Laskowski-Arce MA, Roy CR, (2008) Ankyrin repeat proteins comprise a diverse family of bacterial type IV effectors. Science 320: 1651-1654.
62. Voth DE, Beare PA, Howe D, Sharma UM, Samoilis G, et al. (2011) The Coxiella burnetii cryptic plasmid is enriched in genes encoding type IV secretion system substrates. J Bacteriol 193: 1493-1503.
63. Han GS, O'Hara L, Carman GM, Siniossoglou S, (2008) An unconventional diacylglycerol kinase that regulates phospholipid synthesis and nuclear membrane growth. J Biol Chem 283: 20433-20442.
64. O'Hara L, Han GS, Peak-Chew S, Grimsey N, Carman GM, et al. (2006) Control of phospholipid synthesis by phosphorylation of the yeast lipin Pah1p/Smp2p Mg2+-dependent phosphatidate phosphatase. J Biol Chem 281: 34537-34548.
65. Choi HS, Su WM, Han GS, Plote D, Xu Z, et al. (2012) Pho85p-pho80p phosphorylation of yeast pah1p phosphatidate phosphatase regulates its activity, location, abundance, and function in lipid metabolism. J Biol Chem 287: 11290-11301.
66. Kosodo Y, Imai K, Hirata A, Noda Y, Takatsuki A, et al. (2001) Multicopy suppressors of the sly1 temperature-sensitive mutation in the ER-Golgi vesicular transport in Saccharomyces cerevisiae. Yeast 18: 1003-1014.
67. Han GS, O'Hara L, Siniossoglou S, Carman GM, (2008) Characterization of the yeast DGK1-encoded CTP-dependent diacylglycerol kinase. J Biol Chem 283: 20443-20453.
68. Csaki LS, Reue K, (2010) Lipins: multifunctional lipid metabolism proteins. Annu Rev Nutr 30: 257-272.
69. Santos-Rosa H, Leung J, Grimsey N, Peak-Chew S, Siniossoglou S, (2005) The yeast lipin Smp2 couples phospholipid biosynthesis to nuclear membrane growth. EMBO J 24: 1931-1941.
70. Siniossoglou S, (2009) Lipins, lipids and nuclear envelope structure. Traffic 10: 1181-1187.
71. Han GS, Siniossoglou S, Carman GM, (2007) The cellular functions of the yeast lipin homolog PAH1p are dependent on its phosphatidate phosphatase activity. J Biol Chem 282: 37026-37035.
72. Jenkins GM, Frohman MA, (2005) Phospholipase D: a lipid centric review. Cell Mol Life Sci 62: 2305-2316.
73. Selvy PE, Lavieri RR, Lindsley CW, Brown HA, (2011) Phospholipase D: enzymology, functionality, and chemical modulation. Chem Rev 111: 6064-6119.
74. Sung TC, Roper RL, Zhang Y, Rudge SA, Temel R, et al. (1997) Mutagenesis of phospholipase D defines a superfamily including a trans-Golgi viral protein required for poxvirus pathogenicity. EMBO J 16: 4519-4530.
75. Carrasco S, Merida I, (2004) Diacylglycerol-dependent binding recruits PKCtheta and RasGRP1 C1 domains to specific subcellular localizations in living T lymphocytes. Mol Biol Cell 15: 2932-2942.
76. Gharbi SI, Rincon E, Avila-Flores A, Torres-Ayuso P, Almena M, et al. (2011) Diacylglycerol kinase zeta controls diacylglycerol metabolism at the immunological synapse. Mol Biol Cell 22: 4406-4414.
77. Oancea E, Teruel MN, Quest AF, Meyer T, (1998) Green fluorescent protein (GFP)-tagged cysteine-rich domains from protein kinase C as fluorescent indicators for diacylglycerol signaling in living cells. J Cell Biol 140: 485-498.
78. Wang H, Yang C, Leskow FC, Sun J, Canagarajah B, et al. (2006) Phospholipase Cgamma/diacylglycerol-dependent activation of beta2-chimaerin restricts EGF-induced Rac signaling. EMBO J 25: 2062-2074.
79. Tang BL, Wong SH, Qi XL, Low SH, Hong W, (1993) Molecular cloning, characterization, subcellular localization and dynamics of p23, the mammalian KDEL receptor. J Cell Biol 120: 325-338.
80. Litvak V, Dahan N, Ramachandran S, Sabanay H, Lev S, (2005) Maintenance of the diacylglycerol level in the Golgi apparatus by the Nir2 protein is critical for Golgi secretory function. Nat Cell Biol 7: 225-234.
81. Zeniou-Meyer M, Zabari N, Ashery U, Chasserot-Golaz S, Haeberle AM, et al. (2007) Phospholipase D1 production of phosphatidic acid at the plasma membrane promotes exocytosis of large dense-core granules at a late stage. J Biol Chem 282: 21746-21757.
82. Nakanishi H, de los Santos P, Neiman AM, (2004) Positive and negative regulation of a SNARE protein by control of intracellular localization. Mol Biol Cell 15: 1802-1815.
83. Morris AJ, Frohman MA, Engebrecht J, (1997) Measurement of phospholipase D activity. Anal Biochem 252: 1-9.
84. Nanjundan M, Possmayer F, (2003) Pulmonary phosphatidic acid phosphatase and lipid phosphate phosphohydrolase. Am J Physiol Lung Cell Mol Physiol 284: L1-23.
85. Newton HJ, Ang DK, van Driel IR, Hartland EL, (2010) Molecular pathogenesis of infections caused by Legionella pneumophila. Clin Microbiol Rev 23: 274-298.
86. Neunuebel MR, Chen Y, Gaspar AH, Backlund PS Jr, Yergey A, et al. (2011) De-AMPylation of the small GTPase Rab1 by the pathogen Legionella pneumophila. Science 333: 453-456.
87. McDermott M, Wakelam MJ, Morris AJ, (2004) Phospholipase D. Biochem Cell Biol 82: 225-253.
88. Ragaz C, Pietsch H, Urwyler S, Tiaden A, Weber SS, et al. (2008) The Legionella pneumophila phosphatidylinositol-4 phosphate-binding type IV substrate SidC recruits endoplasmic reticulum vesicles to a replication-permissive vacuole. Cell Microbiol 10: 2416-2433.
89. Van Meer G, Voelker DR, Feigenson GW, (2008) Membrane lipids: where they are and how they behave. Nat Rev Mol Cell Biol 9: 112-124.
90. Graham TR, Burd CG, (2010) Coordination of Golgi functions by phosphatidylinositol 4-kinases. Trends Cell Biol 21: 113-121.
91. Fu Y, Rubin CS, (2011) Protein kinase D: coupling extracellular stimuli to the regulation of cell physiology. EMBO Rep 12: 785-796.
92. Almena M, Merida I, (2011) Shaping up the membrane: diacylglycerol coordinates spatial orientation of signaling. Trends Biochem Sci 36: 593-603.
93. Sadosky AB, Wiater LA, Shuman HA, (1993) Identification of Legionella pneumophila genes required for growth within and killing of human macrophages. Infect Immun 61: 5361-5373.
94. Casadaban MJ, Chou J, Cohen SN, (1980) In vitro gene fusions that join an enzymatically active beta-galactosidase segment to amino-terminal fragments of exogenous proteins: Escherichia coli plasmid vectors for the detection and cloning of translational initiation signals. J Bacteriol 143: 971-980.
95. Brachmann CB, Davies A, Cost GJ, Caputo E, Li J, et al. (1998) Designer deletion strains derived from Saccharomyces cerevisiae S288C: a useful set of strains and plasmids for PCR-mediated gene disruption and other applications. Yeast 14: 115-132.
96. Thomas BJ, Rothstein R, (1989) Elevated recombination rates in transcriptionally active DNA. Cell 56: 619-630.
97. Giaever G, Chu AM, Ni L, Connelly C, Riles L, et al. (2002) Functional profiling of the Saccharomyces cerevisiae genome. Nature 418: 387-391.
98. Zusman T, Aloni G, Halperin E, Kotzer H, Degtyar E, et al. (2007) The response regulator PmrA is a major regulator of the icm/dot type IV secretion system in Legionella pneumophila and Coxiella burnetii. Mol Microbiol 63: 1508-1523.
99. Jansen G, Wu C, Schade B, Thomas DY, Whiteway M, (2005) Drag&Drop cloning in yeast. Gene 344: 43-51.
100. Knop M, Siegers K, Pereira G, Zachariae W, Winsor B, et al. (1999) Epitope tagging of yeast genes using a PCR-based strategy: more tags and improved practical routines. Yeast 15: 963-972.
101. Sabo Y, Ehrlich M, Bacharach E, (2011) The conserved YAGL motif in human metapneumovirus is required for higher-order cellular assemblies of the matrix protein and for virion production. J Virol 85: 6594-6609.
102. Segal G, Shuman HA, (1997) Characterization of a new region required for macrophage killing by Legionella pneumophila. Infect Immun 65: 5057-5066.
103. Segal G, Shuman HA, (1999) Legionella pneumophila utilize the same genes to multiply within Acanthamoeba castellanii and human macrophages. Infect Immun 67: 2117-2124.
104. Voth WP, Jiang YW, Stillman DJ, (2003) New 'marker swap' plasmids for converting selectable markers on budding yeast gene disruptions and plasmids. Yeast 20: 985-993.
105. Gietz RD, Woods RA, (2002) Transformation of yeast by lithium acetate/single-stranded carrier DNA/polyethylene glycol method. Methods Enzymol 350: 87-96.
106. Ho SN, Hunt HD, Horton RM, Pullen JK, Pease LR, (1989) Site-directed mutagenesis by overlap extension using the polymerase chain reaction. Gene 77: 51-59.
107. Carlson M, Botstein D, (1982) Two differentially regulated mRNAs with different 5′ ends encode secreted with intracellular forms of yeast invertase. Cell 28: 145-154.