A Phospholipase Is Involved in Disruption of the Liver Stage Parasitophorous Vacuole Membrane
Leaving their host cell is a crucial process for intracellular pathogens, allowing successful infection of other cells and thereby spreading of infection. Plasmodium parasites infect hepatocytes and red blood cells, and inside these cells they are contained within a vacuole like many other intracellular pathogens. Before parasites can infect other cells, the surrounding parasitophorous vacuole membrane (PVM) needs to be ruptured. However, little is known about this process on a molecular level and Plasmodium proteins mediating lysis of the PVM during parasite egress have not so far been identified. In this study, we characterize a Plasmodium phospholipase and show that it localizes to the PVM of parasites within hepatocytes. We demonstrate that parasites lacking this protein have a defect in rupture of the PVM and thereby in host cell egress. In conclusion, our study shows for the first time that a phospholipase plays a role in PVM disruption of an intracellular eukaryotic parasite.
Vyšlo v časopise:
A Phospholipase Is Involved in Disruption of the Liver Stage Parasitophorous Vacuole Membrane. PLoS Pathog 11(3): e32767. doi:10.1371/journal.ppat.1004760
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1004760
Souhrn
Leaving their host cell is a crucial process for intracellular pathogens, allowing successful infection of other cells and thereby spreading of infection. Plasmodium parasites infect hepatocytes and red blood cells, and inside these cells they are contained within a vacuole like many other intracellular pathogens. Before parasites can infect other cells, the surrounding parasitophorous vacuole membrane (PVM) needs to be ruptured. However, little is known about this process on a molecular level and Plasmodium proteins mediating lysis of the PVM during parasite egress have not so far been identified. In this study, we characterize a Plasmodium phospholipase and show that it localizes to the PVM of parasites within hepatocytes. We demonstrate that parasites lacking this protein have a defect in rupture of the PVM and thereby in host cell egress. In conclusion, our study shows for the first time that a phospholipase plays a role in PVM disruption of an intracellular eukaryotic parasite.
Zdroje
1. Hybiske K, Stephens RS (2008) Exit strategies of intracellular pathogens. Nat Rev Microbiol 6: 99–110. doi: 10.1038/nrmicro1821 18197167
2. Friedrich N, Hagedorn M, Soldati-Favre D, Soldati T (2012) Prison break: pathogens' strategies to egress from host cells. Microbiol Mol Biol Rev 76: 707–720. doi: 10.1128/MMBR.00024-12 23204363
3. Ward GE, Miller LH, Dvorak JA (1993) The origin of parasitophorous vacuole membrane lipids in malaria-infected erythrocytes. J Cell Sci 106 (Pt 1): 237–248.
4. Spielmann T, Montagna GN, Hecht L, Matuschewski K (2012) Molecular make-up of the Plasmodium parasitophorous vacuolar membrane. Int J Med Microbiol 302: 179–186. doi: 10.1016/j.ijmm.2012.07.011 22898489
5. Sturm A, Amino R, van de Sand C, Regen T, Retzlaff S, et al. (2006) Manipulation of host hepatocytes by the malaria parasite for delivery into liver sinusoids. Science 313: 1287–1290. 16888102
6. Yeoh S, O'Donnell RA, Koussis K, Dluzewski AR, Ansell KH, et al. (2007) Subcellular discharge of a serine protease mediates release of invasive malaria parasites from host erythrocytes. Cell 131: 1072–1083. 18083098
7. Schmidt-Christensen A, Sturm A, Horstmann S, Heussler VT (2008) Expression and processing of Plasmodium berghei SERA3 during liver stages. Cell Microbiol 10: 1723–1734. doi: 10.1111/j.1462-5822.2008.01162.x 18419771
8. Putrianti ED, Schmidt-Christensen A, Arnold I, Heussler VT, Matuschewski K, et al. (2010) The Plasmodium serine-type SERA proteases display distinct expression patterns and non-essential in vivo roles during life cycle progression of the malaria parasite. Cell Microbiol 12: 725–739. doi: 10.1111/j.1462-5822.2009.01419.x 20039882
9. Arastu-Kapur S, Ponder EL, Fonovic UP, Yeoh S, Yuan F, et al. (2008) Identification of proteases that regulate erythrocyte rupture by the malaria parasite Plasmodium falciparum. Nat Chem Biol 4: 203–213. doi: 10.1038/nchembio.70 18246061
10. Suarez C, Volkmann K, Gomes AR, Billker O, Blackman MJ (2013) The malarial serine protease SUB1 plays an essential role in parasite liver stage development. PLoS Pathog 9: e1003811. doi: 10.1371/journal.ppat.1003811 24348254
11. Tawk L, Lacroix C, Gueirard P, Kent R, Gorgette O, et al. (2013) A key role for Plasmodium subtilisin-like SUB1 protease in egress of malaria parasites from host hepatocytes. J Biol Chem 288: 33336–33346. doi: 10.1074/jbc.M113.513234 24089525
12. Kaiser K, Camargo N, Coppens I, Morrisey JM, Vaidya AB, et al. (2004) A member of a conserved Plasmodium protein family with membrane-attack complex/perforin (MACPF)-like domains localizes to the micronemes of sporozoites. Mol Biochem Parasitol 133: 15–26. 14668008
13. Garg S, Agarwal S, Kumar S, Yazdani SS, Chitnis CE, et al. (2013) Calcium-dependent permeabilization of erythrocytes by a perforin-like protein during egress of malaria parasites. Nat Commun 4: 1736. doi: 10.1038/ncomms2725 23591903
14. Deligianni E, Morgan RN, Bertuccini L, Wirth CC, Silmon de Monerri NC, et al. (2013) A perforin-like protein mediates disruption of the erythrocyte membrane during egress of Plasmodium berghei male gametocytes. Cell Microbiol 15: 1438–1455. doi: 10.1111/cmi.12131 23461714
15. Wirth CC, Glushakova S, Scheuermayer M, Repnik U, Garg S, et al. (2014) Perforin-like protein PPLP2 permeabilizes the red blood cell membrane during egress of Plasmodium falciparum gametocytes. Cell Microbiol 16: 709–733. doi: 10.1111/cmi.12288 24602217
16. Dvorin JD, Martyn DC, Patel SD, Grimley JS, Collins CR, et al. (2010) A plant-like kinase in Plasmodium falciparum regulates parasite egress from erythrocytes. Science 328: 910–912. doi: 10.1126/science.1188191 20466936
17. Falae A, Combe A, Amaladoss A, Carvalho T, Menard R, et al. (2010) Role of Plasmodium berghei cGMP-dependent protein kinase in late liver stage development. J Biol Chem 285: 3282–3288. doi: 10.1074/jbc.M109.070367 19940133
18. Ishino T, Boisson B, Orito Y, Lacroix C, Bischoff E, et al. (2009) LISP1 is important for the egress of Plasmodium berghei parasites from liver cells. Cell Microbiol 11: 1329–1339. doi: 10.1111/j.1462-5822.2009.01333.x 19438514
19. Smith GA, Marquis H, Jones S, Johnston NC, Portnoy DA, et al. (1995) The two distinct phospholipases C of Listeria monocytogenes have overlapping roles in escape from a vacuole and cell-to-cell spread. Infect Immun 63: 4231–4237. 7591052
20. Whitworth T, Popov VL, Yu XJ, Walker DH, Bouyer DH (2005) Expression of the Rickettsia prowazekii pld or tlyC gene in Salmonella enterica serovar Typhimurium mediates phagosomal escape. Infect Immun 73: 6668–6673. 16177343
21. Raabe AC, Wengelnik K, Billker O, Vial HJ (2011) Multiple roles for Plasmodium berghei phosphoinositide-specific phospholipase C in regulating gametocyte activation and differentiation. Cell Microbiol 13: 955–966. doi: 10.1111/j.1462-5822.2011.01591.x 21518218
22. Carey AF, Singer M, Bargieri D, Thiberge S, Frischknecht F, et al. (2014) Calcium dynamics of Plasmodium berghei sporozoite motility. Cell Microbiol 16: 768–783. doi: 10.1111/cmi.12289 24617597
23. Agarwal S, Singh MK, Garg S, Chitnis CE, Singh S (2013) Ca(2+)-mediated exocytosis of subtilisin-like protease 1: a key step in egress of Plasmodium falciparum merozoites. Cell Microbiol 15: 910–921. doi: 10.1111/cmi.12086 23217145
24. Raabe A, Berry L, Sollelis L, Cerdan R, Tawk L, et al. (2011) Genetic and transcriptional analysis of phosphoinositide-specific phospholipase C in Plasmodium. Exp Parasitol 129: 75–80. doi: 10.1016/j.exppara.2011.05.023 21651909
25. Bhanot P, Schauer K, Coppens I, Nussenzweig V (2005) A surface phospholipase is involved in the migration of plasmodium sporozoites through cells. J Biol Chem 280: 6752–6760. 15590623
26. Helm S, Lehmann C, Nagel A, Stanway RR, Horstmann S, et al. (2010) Identification and characterization of a liver stage-specific promoter region of the malaria parasite Plasmodium. PLoS One 5: e13653. doi: 10.1371/journal.pone.0013653 21048918
27. Godiska R, Mead D, Dhodda V, Wu C, Hochstein R, et al. (2010) Linear plasmid vector for cloning of repetitive or unstable sequences in Escherichia coli. Nucleic Acids Res 38: e88. doi: 10.1093/nar/gkp1181 20040575
28. Pfander C, Anar B, Schwach F, Otto TD, Brochet M, et al. (2011) A scalable pipeline for highly effective genetic modification of a malaria parasite. Nat Methods 8: 1078–1082. doi: 10.1038/nmeth.1742 22020067
29. Ramakrishnan C, Rademacher A, Soichot J, Costa G, Waters AP, et al. (2012) Salivary gland-specific P. berghei reporter lines enable rapid evaluation of tissue-specific sporozoite loads in mosquitoes. PLoS One 7: e36376. doi: 10.1371/journal.pone.0036376 22574152
30. Graewe S, Rankin KE, Lehmann C, Deschermeier C, Hecht L, et al. (2011) Hostile takeover by Plasmodium: reorganization of parasite and host cell membranes during liver stage egress. PLoS Pathog 7: e1002224. doi: 10.1371/journal.ppat.1002224 21909271
31. Blackman MJ, Carruthers VB (2013) Recent insights into apicomplexan parasite egress provide new views to a kill. Curr Opin Microbiol 16: 459–464. doi: 10.1016/j.mib.2013.04.008 23725669
32. Marquis H, Goldfine H, Portnoy DA (1997) Proteolytic pathways of activation and degradation of a bacterial phospholipase C during intracellular infection by Listeria monocytogenes. J Cell Biol 137: 1381–1392. 9182669
33. Rosenstein R, Gotz F (2000) Staphylococcal lipases: biochemical and molecular characterization. Biochimie 82: 1005–1014. 11099797
34. Ruecker A, Shea M, Hackett F, Suarez C, Hirst EM, et al. (2012) Proteolytic activation of the essential parasitophorous vacuole cysteine protease SERA6 accompanies malaria parasite egress from its host erythrocyte. J Biol Chem 287: 37949–37963. doi: 10.1074/jbc.M112.400820 22984267
35. Stallmach R, Kavishwar M, Withers-Martinez C, Hackett F, Collins CR, et al. (2015) Plasmodium falciparum SERA5 plays a non-enzymatic role in the malarial asexual blood-stage lifecycle. Mol Microbiol.
36. Goebel W, Kuhn M (2000) Bacterial replication in the host cell cytosol. Curr Opin Microbiol 3: 49–53. 10679420
37. Kadota K, Ishino T, Matsuyama T, Chinzei Y, Yuda M (2004) Essential role of membrane-attack protein in malarial transmission to mosquito host. Proc Natl Acad Sci U S A 101: 16310–16315. 15520375
38. Ecker A, Pinto SB, Baker KW, Kafatos FC, Sinden RE (2007) Plasmodium berghei: plasmodium perforin-like protein 5 is required for mosquito midgut invasion in Anopheles stephensi. Exp Parasitol 116: 504–508. 17367780
39. Ishino T, Chinzei Y, Yuda M (2005) A Plasmodium sporozoite protein with a membrane attack complex domain is required for breaching the liver sinusoidal cell layer prior to hepatocyte infection. Cell Microbiol 7: 199–208. 15659064
40. Andrews NW, Abrams CK, Slatin SL, Griffiths G (1990) A T. cruzi-secreted protein immunologically related to the complement component C9: evidence for membrane pore-forming activity at low pH. Cell 61: 1277–1287. 2194668
41. Noronha FS, Cruz JS, Beirao PS, Horta MF (2000) Macrophage damage by Leishmania amazonensis cytolysin: evidence of pore formation on cell membrane. Infect Immun 68: 4578–4584. 10899858
42. Kafsack BF, Pena JD, Coppens I, Ravindran S, Boothroyd JC, et al. (2009) Rapid membrane disruption by a perforin-like protein facilitates parasite exit from host cells. Science 323: 530–533. doi: 10.1126/science.1165740 19095897
43. Sheffield P, Garrard S, Derewenda Z (1999) Overcoming expression and purification problems of RhoGDI using a family of "parallel" expression vectors. Protein Expr Purif 15: 34–39. 10024467
44. Lin JW, Annoura T, Sajid M, Chevalley-Maurel S, Ramesar J, et al. (2011) A novel 'gene insertion/marker out' (GIMO) method for transgene expression and gene complementation in rodent malaria parasites. PLoS One 6: e29289. doi: 10.1371/journal.pone.0029289 22216235
45. Graewe S, Retzlaff S, Struck N, Janse CJ, Heussler VT (2009) Going live: a comparative analysis of the suitability of the RFP derivatives RedStar, mCherry and tdTomato for intravital and in vitro live imaging of Plasmodium parasites. Biotechnol J 4: 895–902. doi: 10.1002/biot.200900035 19492329
46. Janse CJ, Ramesar J, Waters AP (2006) High-efficiency transfection and drug selection of genetically transformed blood stages of the rodent malaria parasite Plasmodium berghei. Nat Protoc 1: 346–356. 17406255
47. Orr RY, Philip N, Waters AP (2012) Improved negative selection protocol for Plasmodium berghei in the rodent malarial model. Malar J 11: 103. doi: 10.1186/1475-2875-11-103 22463060
48. Stanway RR, Graewe S, Rennenberg A, Helm S, Heussler VT (2009) Highly efficient subcloning of rodent malaria parasites by injection of single merosomes or detached cells. Nat Protoc 4: 1433–1439. doi: 10.1038/nprot.2009.172 19745825
49. Sebastian S, Brochet M, Collins MO, Schwach F, Jones ML, et al. (2012) A Plasmodium calcium-dependent protein kinase controls zygote development and transmission by translationally activating repressed mRNAs. Cell Host Microbe 12: 9–19. doi: 10.1016/j.chom.2012.05.014 22817984
50. Delves MJ, Sinden RE (2010) A semi-automated method for counting fluorescent malaria oocysts increases the throughput of transmission blocking studies. Malar J 9: 35. doi: 10.1186/1475-2875-9-35 20113492
51. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25: 402–408. 11846609
52. Eickel N, Kaiser G, Prado M, Burda PC, Roelli M, et al. (2013) Features of autophagic cell death in Plasmodium liver-stage parasites. Autophagy 9: 568–580. doi: 10.4161/auto.23689 23388496
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Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
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