Legionella pneumophila effector LpdA Is a palmitoylated phospholipase D virulence factor

Infection and Immunity

Volumn 83, Issue 10, 2015, Pages 3989-4002

  Schroeder, Gunnar N ^a   Aurass, Philipp ^b   Oates, Clare V ^c   Tate, Edward W ^a   Hartland, Elizabeth L ^c   Flieger, Antje ^b   Frankel, Gad ^a  

^a IMPERIAL COLLEGE LONDON   (United Kingdom)

^b ROBERT KOCH INSTITUTE   (Germany)

^c UNIVERSITY OF MELBOURNE   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

BACTERIAL PROTEIN; CALNEXIN; LPDA PROTEIN; PHOSPHATIDIC ACID; PHOSPHATIDYLGLYCEROL; PHOSPHATIDYLINOSITOL; PHOSPHATIDYLINOSITOL 3 PHOSPHATE; PHOSPHATIDYLINOSITOL 4 PHOSPHATE; PHOSPHOLIPASE D; RAB PROTEIN; UNCLASSIFIED DRUG; VIRULENCE FACTOR;

AMINO ACID SUBSTITUTION; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; AUTOPHAGOSOME; BACTERIAL LOAD; BACTERIAL VIRULENCE; CELL CULTURE; CELL DISRUPTION; CELL MEMBRANE; CELL MIGRATION; CELL VACUOLE; CELLULAR DISTRIBUTION; CONTROLLED STUDY; ENDOSOME; ENZYME SPECIFICITY; FEMALE; GOLGI COMPLEX; GOLGI MEMBRANE; HOST CELL; HUMAN; HUMAN CELL; HYDROLYSIS; IN VITRO STUDY; LEGIONELLA PNEUMOPHILA; LEGIONNAIRE DISEASE; LIPID COMPOSITION; LIPID TRANSPORT; MITOCHONDRION; MOUSE; MUTANT; NONHUMAN; PALMITOYLATION; PHAGOLYSOSOME; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; PROTEIN PROCESSING; PROTEIN TRANSPORT; SECRETORY PATHWAY; TRANSPORT VESICLE; WESTERN BLOTTING; ANIMAL; ENZYMOLOGY; GENETICS; LIPOYLATION; METABOLISM; MICROBIOLOGY;

ANIMALS; BACTERIAL PROTEINS; CELL MEMBRANE; HUMANS; LEGIONELLA PNEUMOPHILA; LEGIONNAIRES' DISEASE; LIPOYLATION; MICE; PHOSPHOLIPASE D; PROTEIN TRANSPORT; VACUOLES; VIRULENCE FACTORS;

EID: 84944446943     PISSN: 00199567     EISSN: 10985522     Source Type: Journal    
DOI: 10.1128/IAI.00785-15     Document Type: Article

References (68)

1. Newton HJ, Ang DK, van Driel IR, Hartland EL. 2010. Molecular pathogenesis of infections caused by Legionella pneumophila. Clin Microbiol Rev 23:274-298. http://dx.doi.org/10.1128/CMR.00052-09.
2. Allombert J, Fuche F, Michard C, Doublet P. 2013. Molecular mimicry and original biochemical strategies for the biogenesis of a Legionella pneumophila replicative niche in phagocytic cells. Microbes Infect 15:981-988. http://dx.doi.org/10.1016/j.micinf.2013.09.007.
3. Fuche F, Vianney A, Andrea C, Doublet P, Gilbert C. 2015. Functional type 1 secretion system involved in Legionella pneumophila virulence. J Bacteriol 197:563-571. http://dx.doi.org/10.1128/JB.02164-14.
4. Rossier O, Starkenburg SR, Cianciotto NP. 2004. Legionella pneumophila type II protein secretion promotes virulence in the A/J mouse model of Legionnaires' disease pneumonia. Infect Immun 72:310-321. http://dx.doi.org/10.1128/IAI.72.1.310-321.2004.
5. Segal G, Purcell M, Shuman HA. 1998. Host cell killing and bacterial conjugation require overlapping sets of genes within a 22-kb region of the Legionella pneumophila genome. Proc Natl Acad Sci U S A 95:1669-1674. http://dx.doi.org/10.1073/pnas.95.4.1669.
6. Vogel JP, Andrews HL, Wong SK, Isberg RR. 1998. Conjugative transfer by the virulence system of Legionella pneumophila. Science 279:873-876. http://dx.doi.org/10.1126/science.279.5352.873.
7. Lifshitz Z, Burstein D, Peeri M, Zusman T, Schwartz K, Shuman HA, Pupko T, Segal G. 2013. Computational modeling and experimental validation of the Legionella and Coxiella virulence-related type IVB secre-tion signal. Proc Natl Acad Sci U S A 110:E707-E715. http://dx.doi.org/10.1073/pnas.1215278110.
8. Zhu W, Banga S, Tan Y, Zheng C, Stephenson R, Gately J, Luo ZQ. 2011. Comprehensive identification of protein substrates of the Dot/Icm type IV transporter of Legionella pneumophila. PLoS One 6:e17638. http://dx.doi.org/10.1371/journal.pone.0017638.
9. Horwitz MA. 1983. Formation of a novel phagosome by the Legionnaires' disease bacterium (Legionella pneumophila) in human monocytes. J Exp Med 158:1319-1331. http://dx.doi.org/10.1084/jem.158.4.1319.
10. Kagan JC, Roy CR. 2002. Legionella phagosomes intercept vesicular traffic from endoplasmic reticulum exit sites. Nat Cell Biol 4:945-954. http://dx.doi.org/10.1038/ncb883.
11. Swanson MS, Isberg RR. 1995. Association of Legionella pneumophila with the macrophage endoplasmic reticulum. Infect Immun 63:3609-3620.
12. Prashar A, Terebiznik MR. 2015. Legionella pneumophila: homeward bound away from the phagosome. Curr Opin Microbiol 23:86-93. http://dx.doi.org/10.1016/j.mib.2014.11.008.
13. So EC, Mattheis C, Tate EW, Frankel G, Schroeder GN. 2015. Creating a customized intracellular niche: subversion of host cell signaling by Legionella type IV secretion system effectors. Can J Microbiol 6:1-19.
14. Goody RS, Itzen A. 2013. Modulation of small GTPases by Legionella. Curr Top Microbiol Immunol 376:117-133. http://dx.doi.org/10.1007/82_2013_340.
15. Mousnier A, Schroeder GN, Stoneham CA, So EC, Garnett JA, Yu L, Matthews SJ, Choudhary JS, Hartland EL, Frankel G. 2014. A new method to determine in vivo interactomes reveals binding of the Legionella pneumophila effector PieE to multiple Rab GTPases. mBio 5:e01148-14. http://dx.doi.org/10.1128/mBio.01148-14.
16. Haneburger I, Hilbi H. 2013. Phosphoinositide lipids and the Legionella pathogen vacuole. Curr Top Microbiol Immunol 376:155-173. http://dx.doi.org/10.1007/82_2013_341.
17. Ivanov SS, Roy C. 2013. Host lipidation: a mechanism for spatial regulation of Legionella effectors. Curr Top Microbiol Immunol 376:135-154. http://dx.doi.org/10.1007/82_2013_344.
18. Lang C, Flieger A. 2011. Characterisation of Legionella pneumophila phospholipases and their impact on host cells. Eur J Cell Biol 90:903-912. http://dx.doi.org/10.1016/j.ejcb.2010.12.003.
19. Ivanov SS, Charron G, Hang HC, Roy CR. 2010. Lipidation by the host prenyltransferase machinery facilitates membrane localization of Legionella pneumophila effector proteins. J Biol Chem 285:34686-34698. http://dx.doi.org/10.1074/jbc. M110.170746.
20. 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. http://dx.doi.org/10.1084/jem.20100771.
21. Harding CR, Mattheis C, Mousnier A, Oates CV, Hartland EL, Frankel G, Schroeder GN. 2013. LtpD is a novel Legionella pneumophila effector that binds phosphatidylinositol 3-phosphate and inositol monophosphatase IMPA1. Infect Immun 81:4261-4270. http://dx.doi.org/10.1128/IAI.01054-13.
22. Di Paolo G, De Camilli P. 2006. Phosphoinositides in cell regulation and membrane dynamics. Nature 443:651-657. http://dx.doi.org/10.1038/nature05185.
23. Hsu F, Zhu W, Brennan L, Tao L, Luo ZQ, Mao Y. 2012. Structural basis for substrate recognition by a unique Legionella phosphoinositide phosphatase. Proc Natl Acad Sci U S A 109:13567-13572. http://dx.doi.org/10.1073/pnas.1207903109.
24. Toulabi L, Wu X, Cheng Y, Mao Y. 2013. Identification and structural characterization of a Legionella phosphoinositide phosphatase. J Biol Chem 288:24518-24527. http://dx.doi.org/10.1074/jbc. M113.474239.
25. Gaspar AH, Machner MP. 2014. VipD is a Rab5-activated phospholipase A1 that protects Legionella pneumophila from endosomal fusion. Proc Natl Acad Sci U S A 111:4560-4565. http://dx.doi.org/10.1073/pnas.1316376111.
26. Schunder E, Adam P, Higa F, Remer KA, Lorenz U, Bender J, Schulz T, Flieger A, Steinert M, Heuner K. 2010. Phospholipase PlaB is a new virulence factor of Legionella pneumophila. Int J Med Microbiol 300:313-323. http://dx.doi.org/10.1016/j.ijmm.2010.01.002.
27. Aurass P, Schlegel M, Metwally O, Harding CR, Schroeder GN, Frankel G, Flieger A. 2013. The Legionella pneumophila Dot/Icm-secreted effector PlcC/CegC1 together with PlcA and PlcB promotes virulence and belongs to a novel zinc metallophospholipase C family present in bacteria and fungi. J Biol Chem 288:11080-11092. http://dx.doi.org/10.1074/jbc. M112.426049.
28. Viner R, Chetrit D, Ehrlich M, Segal G. 2012. Identification of two Legionella pneumophila effectors that manipulate host phospholipids biosynthesis. PLoS Pathog 8:e1002988. http://dx.doi.org/10.1371/journal.ppat.1002988.
29. Jenkins GM, Frohman MA. 2005. Phospholipase D: a lipid centric review. Cell Mol Life Sci 62:2305-2316. http://dx.doi.org/10.1007/s00018-005-5195-z.
30. Edelstein PH. 1986. Control of Legionella in hospitals. J Hosp Infect 8:109-115. http://dx.doi.org/10.1016/0195-6701(86)90037-X.
31. Engleberg NC, Drutz DJ, Eisenstein BI. 1984. Cloning and expression of Legionella pneumophila antigens in Escherichia coli. Infect Immun 44:222-227.
32. Schroeder GN, Petty NK, Mousnier A, Harding CR, Vogrin AJ, Wee B, Fry NK, Harrison TG, Newton HJ, Thomson NR, Beatson SA, Dougan G, Hartland EL, Frankel G. 2010. Legionella pneumophila strain 130b possesses a unique combination of type IV secretion systems and novel Dot/Icm secretion system effector proteins. J Bacteriol 192:6001-6016. http://dx.doi.org/10.1128/JB.00778-10.
33. Chen DQ, Huang SS, Lu YJ. 2006. Efficient transformation of Legionella pneumophila by high-voltage electroporation. Microbiol Res 161:246-251. http://dx.doi.org/10.1016/j.micres.2005.09.001.
34. Galan JE, Ginocchio C, Costeas P. 1992. Molecular and functional characterization of the Salmonella invasion gene invA: homology of InvA to members of a new protein family. J Bacteriol 174:4338-4349.
35. Stone BJ, Kwaik YA. 1999. Natural competence for DNA transformation by Legionella pneumophila and its association with expression of type IV pili. J Bacteriol 181:1395-1402.
36. Shenoy AR, Wellington DA, Kumar P, Kassa H, Booth CJ, Cresswell P, MacMicking JD. 2012. GBP5 promotes NLRP3 inflammasome assembly and immunity in mammals. Science 336:481-485. http://dx.doi.org/10.1126/science.1217141.
37. Bligh EG, Dyer WJ. 1959. A rapid method of total lipid extraction and purification. Can J Biochem Physiol 37:911-917. http://dx.doi.org/10.1139/o59-099.
38. Heal WP, Jovanovic B, Bessin S, Wright MH, Magee AI, Tate EW. 2011. Bio-orthogonal chemical tagging of protein cholesterylation in living cells. Chem Commun 47:4081-4083. http://dx.doi.org/10.1039/c0cc04710d.
39. Heal WP, Wright MH, Thinon E, Tate EW. 2012. Multifunctional protein labeling via enzymatic N-terminal tagging and elaboration by click chemistry. Nat Protoc 7:105-117. http://dx.doi.org/10.1038/nprot.2011.425.
40. Hovel-Miner G, Pampou S, Faucher SP, Clarke M, Morozova I, Morozov P, Russo JJ, Shuman HA, Kalachikov S. 2009. SigmaS controls multiple pathways associated with intracellular multiplication of Legionella pneumophila. J Bacteriol 191:2461-2473. http://dx.doi.org/10.1128/JB.01578-08.
41. Harding CR, Stoneham CA, Schuelein R, Newton H, Oates CV, Hartland EL, Schroeder GN, Frankel G. 2013. The Dot/Icm effector SdhA is necessary for virulence of Legionella pneumophila in Galleria mellonella and A/J mice. Infect Immun 81:2598-2605. http://dx.doi.org/10.1128/IAI.00296-13.
42. Chien M, Morozova I, Shi S, Sheng H, Chen J, Gomez SM, Asamani G, Hill K, Nuara J, Feder M, Rineer J, Greenberg JJ, Steshenko V, Park SH, Zhao B, Teplitskaya E, Edwards JR, Pampou S, Georghiou A, Chou IC, Iannuccilli W, Ulz ME, Kim DH, Geringer-Sameth A, Goldsberry C, Morozov P, Fischer SG, Segal G, Qu X, Rzhetsky A, Zhang P, Cayanis E, De Jong PJ, Ju J, Kalachikov S, Shuman HA, Russo JJ. 2004. The genomic sequence of the accidental pathogen Legionella pneumophila. Science 305:1966-1968. http://dx.doi.org/10.1126/science.1099776.
43. Steinert M, Heuner K, Buchrieser C, Albert-Weissenberger C, Glockner G. 2007. Legionella pathogenicity: genome structure, regulatory networks and the host cell response. Int J Med Microbiol 297:577-587. http://dx.doi.org/10.1016/j.ijmm.2007.03.009.
44. D'Auria G, Jimenez-Hernandez N, Peris-Bondia F, Moya A, Latorre A. 2010. Legionella pneumophila pangenome reveals strain-specific virulence factors. BMC Genomics 11:181. http://dx.doi.org/10.1186/1471-2164-11-181.
45. Cazalet C, Rusniok C, Bruggemann H, Zidane N, Magnier A, Ma L, Tichit M, Jarraud S, Bouchier C, Vandenesch F, Kunst F, Etienne J, Glaser P, Buchrieser C. 2004. Evidence in the Legionella pneumophila genome for exploitation of host cell functions and high genome plasticity. Nat Genet 36:1165-1173. http://dx.doi.org/10.1038/ng1447.
46. Kassas N, Tryoen-Toth P, Corrotte M, Thahouly T, Bader MF, Grant NJ, Vitale N. 2012. Genetically encoded probes for phosphatidic acid. Methods Cell Biol 108:445-459. http://dx.doi.org/10.1016/B978-0-12-386487-1.00020-1.
47. Ren J, Wen L, Gao X, Jin C, Xue Y, Yao X. 2008. CSS-Palm 2.0: an updated software for palmitoylation sites prediction. Protein Eng Des Sel 21:639-644. http://dx.doi.org/10.1093/protein/gzn039.
48. Tate EW, Kalesh KA, Lanyon-Hogg T, Storck EM, Thinon E. 2015. Global profiling of protein lipidation using chemical proteomic technologies. Curr Opin Chem Biol 24C:48-57. http://dx.doi.org/10.1016/j.cbpa.2014.10.016.
49. Martin BR, Cravatt BF. 2009. Large-scale profiling of protein palmitoylation in mammalian cells. Nat Methods 6:135-138. http://dx.doi.org/10.1038/nmeth.1293.
50. 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. http://dx.doi.org/10.1038/nrm2330.
51. De Matteis MA, Wilson C, D'Angelo G. 2013. Phosphatidylinositol-4-phosphate: the Golgi and beyond. Bioessays 35:612-622. http://dx.doi.org/10.1002/bies.201200180.
52. Jeschke A, Zehethofer N, Lindner B, Krupp J, Schwudke D, Haneburger I, Jovic M, Backer JM, Balla T, Hilbi H, Haas A. 2015. Phosphatidylinositol 4-phosphate and phosphatidylinositol 3-phosphate regulate phagolysosome biogenesis. Proc Natl Acad Sci U S A 112:4636-4641. http://dx.doi.org/10.1073/pnas.1423456112.
53. 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 11:1219-1235. http://dx.doi.org/10.1111/j.1462-5822.2009.01328.x.
54. Blanc M, Blaskovic S, van der Goot FG. 2013. Palmitoylation, pathogens and their host. Biochem Soc Trans 41:84-88. http://dx.doi.org/10.1042/BST20120337.
55. Dowen RH, Engel JL, Shao F, Ecker JR, Dixon JE. 2009. A family of bacterial cysteine protease type III effectors utilizes acylation-dependent and -independent strategies to localize to plasma membranes. J Biol Chem 284:15867-15879. http://dx.doi.org/10.1074/jbc. M900519200.
56. Hicks SW, Charron G, Hang HC, Galan JE. 2011. Subcellular targeting of Salmonella virulence proteins by host-mediated S-palmitoylation. Cell Host Microbe 10:9-20. http://dx.doi.org/10.1016/j.chom.2011.06.003.
57. O'Connor TJ, Adepoju Y, Boyd D, Isberg RR. 2011. Minimization of the Legionella pneumophila genome reveals chromosomal regions involved in host range expansion. Proc Natl Acad Sci U S A 108:14733-14740. http://dx.doi.org/10.1073/pnas.1111678108.
58. Fernandez-Moreira E, Helbig JH, Swanson MS. 2006. Membrane vesicles shed by Legionella pneumophila inhibit fusion of phagosomes with lysosomes. Infect Immun 74:3285-3295. http://dx.doi.org/10.1128/IAI.01382-05.
59. Rothmeier E, Pfaffinger G, Hoffmann C, Harrison CF, Grabmayr H, Repnik U, Hannemann M, Wolke S, Bausch A, Griffiths G, Muller- Taubenberger A, Itzen A, Hilbi H. 2013. Activation of Ran GTPase by a Legionella effector promotes microtubule polymerization, pathogen vacuole motility, and infection. PLoS Pathog 9:e1003598. http://dx.doi.org/10.1371/journal.ppat.1003598.
60. Hilbi H, Haas A. 2012. Secretive bacterial pathogens and the secretory pathway. Traffic 13:1187-1197. http://dx.doi.org/10.1111/j.1600-0854.2012.01344.x.
61. Giridharan SS, Cai B, Vitale N, Naslavsky N, Caplan S. 2013. Cooperation of MICAL-L1, syndapin2, and phosphatidic acid in tubular recycling endosome biogenesis. Mol Biol Cell 24:1776-1790. http://dx.doi.org/10.1091/mbc. E13-01-0026.
62. Stamnes M, Schiavo G, Stenbeck G, Sollner TH, Rothman JE. 1998. ADP-ribosylation factor and phosphatidic acid levels in Golgi membranes during budding of coatomer-coated vesicles. Proc Natl Acad Sci U S A 95:13676-13680. http://dx.doi.org/10.1073/pnas.95.23.13676.
63. Yang J-S, Gad H, Lee SY, Mironov A, Zhang L, Beznoussenko GV, Valente C, Turacchio G, Bonsra AN, Du G, Baldanzi G, Graziani A, Bourgoin S, Frohman MA, Luini A, Hsu VW. 2008. A role for phosphatidic acid in COPI vesicle fission yields insights into Golgi maintenance. Nat Cell Biol 10:1146-1153. http://dx.doi.org/10.1038/ncb1774.
64. Siddhanta A, Backer JM, Shields D. 2000. Inhibition of phosphatidic acid synthesis alters the structure of the Golgi apparatus and inhibits secretion in endocrine cells. J Biol Chem 275:12023-12031. http://dx.doi.org/10.1074/jbc.275.16.12023.
65. Riebeling C, Morris AJ, Shields D. 2009. Phospholipase D in the Golgi apparatus. Biochim Biophys Acta 1791:876-880. http://dx.doi.org/10.1016/j.bbalip.2009.04.003.
66. Sonoda H, Okada T, Jahangeer S, Nakamura S. 2007. Requirement of phospholipaseDfor ilimaquinone-induced Golgi membrane fragmentation. J Biol Chem 282:34085-34092. http://dx.doi.org/10.1074/jbc. M705593200.
67. Dolezal P, Aili M, Tong J, Jiang JH, Marobbio CM, Lee SF, Schuelein R, Belluzzo S, Binova E, Mousnier A, Frankel G, Giannuzzi G, Palmieri F, Gabriel K, Naderer T, Hartland EL, Lithgow T. 2012. Legionella pneumophila secretes a mitochondrial carrier protein during infection. PLoS Pathog 8:e1002459. http://dx.doi.org/10.1371/journal.ppat.1002459.
68. de Felipe KS, Glover RT, Charpentier X, Anderson OR, Reyes M, Pericone CD, Shuman HA. 2008. Legionella eukaryotic-like type IV substrates interfere with organelle trafficking. PLoS Pathog 4:e1000117. http://dx.doi.org/10.1371/journal.ppat.1000117.