A Malarial Cysteine Protease is Necessary for Plasmodium Sporozoite Egress from Oocysts

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2005 Jul 20

PMID 16027235

Citations 81

Authors

Ahmed S I Aly

Kai Matuschewski

Affiliations

Soon will be listed here.

Abstract

The Plasmodium life cycle is a sequence of alternating invasive and replicative stages within the vertebrate and invertebrate hosts. How malarial parasites exit their host cells after completion of reproduction remains largely unsolved. Inhibitor studies indicated a role of Plasmodium cysteine proteases in merozoite release from host erythrocytes. To validate a vital function of malarial cysteine proteases in active parasite egress, we searched for target genes that can be analyzed functionally by reverse genetics. Herein, we describe a complete arrest of Plasmodium sporozoite egress from Anopheles midgut oocysts by targeted disruption of a stage-specific cysteine protease. Our findings show that sporozoites exit oocysts by parasite-dependent proteolysis rather than by passive oocyst rupture resulting from parasite growth. We provide genetic proof that malarial cysteine proteases are necessary for egress of invasive stages from their intracellular compartment and propose that similar cysteine protease-dependent mechanisms occur during egress from liver-stage and blood-stage schizonts.

Citing Articles

Post-Translational Modifications of Proteins of Malaria Parasites during the Life Cycle.

Schwarzer E, Skorokhod O Int J Mol Sci. 2024; 25(11).

PMID: 38892332 PMC: 11173270. DOI: 10.3390/ijms25116145.

Plasmodium sporozoite excystation involves local breakdown of the oocyst capsule.

Saeed S, Tremp A, Dessens J Sci Rep. 2023; 13(1):22222.

PMID: 38097730 PMC: 10721906. DOI: 10.1038/s41598-023-49442-1.

Plasmodium GPI-anchored micronemal antigen is essential for parasite transmission through the mosquito host.

Jennison C, Armstrong J, Dankwa D, Hertoghs N, Kumar S, Abatiyow B Mol Microbiol. 2023; 121(3):394-412.

PMID: 37314965 PMC: 11076100. DOI: 10.1111/mmi.15078.

Targetome Analysis of Malaria Sporozoite Transcription Factor AP2-Sp Reveals Its Role as a Master Regulator.

Yuda M, Kaneko I, Murata Y, Iwanaga S, Nishi T mBio. 2023; 14(1):e0251622.

PMID: 36622145 PMC: 9973277. DOI: 10.1128/mbio.02516-22.

The first complete genome of the simian malaria parasite Plasmodium brasilianum.

Bajic M, Ravishankar S, Sheth M, Rowe L, Pacheco M, Patel D Sci Rep. 2022; 12(1):19802.

PMID: 36396703 PMC: 9671904. DOI: 10.1038/s41598-022-20706-6.

References

Salmon B, Oksman A, Goldberg D . Malaria parasite exit from the host erythrocyte: a two-step process requiring extraerythrocytic proteolysis. Proc Natl Acad Sci U S A. 2000; 98(1):271-6. PMC: 14580. DOI: 10.1073/pnas.98.1.271. View

Blackman M . Proteases involved in erythrocyte invasion by the malaria parasite: function and potential as chemotherapeutic targets. Curr Drug Targets. 2001; 1(1):59-83. DOI: 10.2174/1389450003349461. View

Sijwali P, Shenai B, Gut J, Singh A, Rosenthal P . Expression and characterization of the Plasmodium falciparum haemoglobinase falcipain-3. Biochem J. 2001; 360(Pt 2):481-9. PMC: 1222249. DOI: 10.1042/0264-6021:3600481. View

Thathy V, Fujioka H, Gantt S, Nussenzweig R, Nussenzweig V, Menard R . Levels of circumsporozoite protein in the Plasmodium oocyst determine sporozoite morphology. EMBO J. 2002; 21(7):1586-96. PMC: 125957. DOI: 10.1093/emboj/21.7.1586. View

Thathy V, Menard R . Gene targeting in Plasmodium berghei. Methods Mol Med. 2002; 72:317-31. DOI: 10.1385/1-59259-271-6:317. View

Carlton J, Angiuoli S, Suh B, Kooij T, Pertea M, Silva J . Genome sequence and comparative analysis of the model rodent malaria parasite Plasmodium yoelii yoelii. Nature. 2002; 419(6906):512-9. DOI: 10.1038/nature01099. View

Sinden R . Molecular interactions between Plasmodium and its insect vectors. Cell Microbiol. 2002; 4(11):713-24. DOI: 10.1046/j.1462-5822.2002.00229.x. View

Miller S, Good R, Drew D, Delorenzi M, Sanders P, Hodder A . A subset of Plasmodium falciparum SERA genes are expressed and appear to play an important role in the erythrocytic cycle. J Biol Chem. 2002; 277(49):47524-32. DOI: 10.1074/jbc.M206974200. View

Kappe S, Kaiser K, Matuschewski K . The Plasmodium sporozoite journey: a rite of passage. Trends Parasitol. 2003; 19(3):135-43. DOI: 10.1016/s1471-4922(03)00007-2. View

10.

Le Roch K, Zhou Y, Blair P, Grainger M, Moch J, Haynes J . Discovery of gene function by expression profiling of the malaria parasite life cycle. Science. 2003; 301(5639):1503-8. DOI: 10.1126/science.1087025. View

11.

Wickham M, Culvenor J, Cowman A . Selective inhibition of a two-step egress of malaria parasites from the host erythrocyte. J Biol Chem. 2003; 278(39):37658-63. DOI: 10.1074/jbc.M305252200. View

12.

Bozdech Z, Llinas M, Pulliam B, Wong E, Zhu J, DeRisi J . The transcriptome of the intraerythrocytic developmental cycle of Plasmodium falciparum. PLoS Biol. 2003; 1(1):E5. PMC: 176545. DOI: 10.1371/journal.pbio.0000005. View

13.

Sijwali P, Rosenthal P . Gene disruption confirms a critical role for the cysteine protease falcipain-2 in hemoglobin hydrolysis by Plasmodium falciparum. Proc Natl Acad Sci U S A. 2004; 101(13):4384-9. PMC: 384756. DOI: 10.1073/pnas.0307720101. View

14.

Sibley L . Intracellular parasite invasion strategies. Science. 2004; 304(5668):248-53. DOI: 10.1126/science.1094717. View

15.

Sijwali P, Kato K, Seydel K, Gut J, Lehman J, Klemba M . Plasmodium falciparum cysteine protease falcipain-1 is not essential in erythrocytic stage malaria parasites. Proc Natl Acad Sci U S A. 2004; 101(23):8721-6. PMC: 423262. DOI: 10.1073/pnas.0402738101. View

16.

Eksi S, Czesny B, Greenbaum D, Bogyo M, Williamson K . Targeted disruption of Plasmodium falciparum cysteine protease, falcipain 1, reduces oocyst production, not erythrocytic stage growth. Mol Microbiol. 2004; 53(1):243-50. DOI: 10.1111/j.1365-2958.2004.04108.x. View

17.

Vanderberg J . Studies on the motility of Plasmodium sporozoites. J Protozool. 1974; 21(4):527-37. DOI: 10.1111/j.1550-7408.1974.tb03693.x. View

18.

Vanderberg J . Development of infectivity by the Plasmodium berghei sporozoite. J Parasitol. 1975; 61(1):43-50. View

19.

Potocnjak P, Yoshida N, Nussenzweig R, NUSSENZWEIG V . Monovalent fragments (Fab) of monoclonal antibodies to a sporozoite surface antigen (Pb44) protect mice against malarial infection. J Exp Med. 1980; 151(6):1504-13. PMC: 2185881. DOI: 10.1084/jem.151.6.1504. View

20.

Hadley T, Aikawa M, MILLER L . Plasmodium knowlesi: studies on invasion of rhesus erythrocytes by merozoites in the presence of protease inhibitors. Exp Parasitol. 1983; 55(3):306-11. DOI: 10.1016/0014-4894(83)90027-9. View