Gliding Motility of Merozoites

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2021 Nov 25

PMID 34819379

Citations 22

Authors

Kazuhide Yahata

Melissa N Hart

Heledd Davies

Masahito Asada

Samuel C Wassmer

Thomas J Templeton

Moritz Treeck

Robert W Moon

Osamu Kaneko

Affiliations

Soon will be listed here.

Abstract

malaria parasites are obligate intracellular protozoans that use a unique form of locomotion, termed gliding motility, to move through host tissues and invade cells. The process is substrate dependent and powered by an actomyosin motor that drives the posterior translocation of extracellular adhesins which, in turn, propel the parasite forward. Gliding motility is essential for tissue translocation in the sporozoite and ookinete stages; however, the short-lived erythrocyte-invading merozoite stage has never been observed to undergo gliding movement. Here we show merozoites possess the ability to undergo gliding motility in vitro and that this mechanism is likely an important precursor step for successful parasite invasion. We demonstrate that two human infective species, and , have distinct merozoite motility profiles which may reflect distinct invasion strategies. Additionally, we develop and validate a higher throughput assay to evaluate the effects of genetic and pharmacological perturbations on both the molecular motor and the complex signaling cascade that regulates motility in merozoites. The discovery of merozoite motility provides a model to study the glideosome and adds a dimension for work aiming to develop treatments targeting the blood stage invasion pathways.

Citing Articles

Expanding the fluorescent toolkit: Blue fluorescent protein-expressing Plasmodium berghei for enhanced multiplex microscopy.

Atchou K, Caldelari R, Roques M, Schmuckli-Maurer J, Beyeler R, Heussler V PLoS One. 2025; 20(3):e0308055.

PMID: 40029851 PMC: 11875362. DOI: 10.1371/journal.pone.0308055.

Adhesion-driven vesicle translocation through membrane-covered pores.

Baruah N, Midya J, Gompper G, Dasanna A, Auth T Biophys J. 2025; 124(5):740-752.

PMID: 39863923 PMC: 11897550. DOI: 10.1016/j.bpj.2025.01.012.

Emergent actin flows explain distinct modes of gliding motility.

Hueschen C, Segev-Zarko L, Chen J, LeGros M, Larabell C, Boothroyd J Nat Phys. 2024; 20(12):1989-1996.

PMID: 39669527 PMC: 11631758. DOI: 10.1038/s41567-024-02652-4.

Red blood cell signaling is functionally conserved in invasion.

Yong J, Gao X, Prakash P, Ang J, Lai S, Chen M iScience. 2024; 27(10):111052.

PMID: 39635131 PMC: 11615254. DOI: 10.1016/j.isci.2024.111052.

Submicrometre spatiotemporal characterization of the Toxoplasma adhesion strategy for gliding motility.

Vigetti L, Touquet B, Debarre D, Rose T, Bureau L, Abdallah D Nat Microbiol. 2024; 9(12):3148-3164.

PMID: 39496912 DOI: 10.1038/s41564-024-01818-3.

References

Dennis E, Mitchell G, Butcher G, Cohen S . In vitro isolation of Plasmodium knowlesi merozoites using polycarbonate sieves. Parasitology. 1975; 71(3):475-81. DOI: 10.1017/s0031182000047235. View

Geoghegan N, Evelyn C, Whitehead L, Pasternak M, McDonald P, Triglia T . 4D analysis of malaria parasite invasion offers insights into erythrocyte membrane remodeling and parasitophorous vacuole formation. Nat Commun. 2021; 12(1):3620. PMC: 8206130. DOI: 10.1038/s41467-021-23626-7. View

Boucher L, Bosch J . The apicomplexan glideosome and adhesins - Structures and function. J Struct Biol. 2015; 190(2):93-114. PMC: 4417069. DOI: 10.1016/j.jsb.2015.02.008. View

MILLER L, Aikawa M, Johnson J, Shiroishi T . Interaction between cytochalasin B-treated malarial parasites and erythrocytes. Attachment and junction formation. J Exp Med. 1979; 149(1):172-84. PMC: 2184746. DOI: 10.1084/jem.149.1.172. View

Mohring F, Hart M, Rawlinson T, Henrici R, Charleston J, Diez Benavente E . Rapid and iterative genome editing in the malaria parasite provides new tools for research. Elife. 2019; 8. PMC: 6579517. DOI: 10.7554/eLife.45829. View

Bullen H, Jia Y, Yamaryo-Botte Y, Bisio H, Zhang O, Jemelin N . Phosphatidic Acid-Mediated Signaling Regulates Microneme Secretion in Toxoplasma. Cell Host Microbe. 2016; 19(3):349-60. DOI: 10.1016/j.chom.2016.02.006. View

Ishino T, Murata E, Tokunaga N, Baba M, Tachibana M, Thongkukiatkul A . Rhoptry neck protein 2 expressed in Plasmodium sporozoites plays a crucial role during invasion of mosquito salivary glands. Cell Microbiol. 2018; 21(1):e12964. PMC: 6587811. DOI: 10.1111/cmi.12964. View

Russell D, Sinden R . The role of the cytoskeleton in the motility of coccidian sporozoites. J Cell Sci. 1981; 50:345-59. DOI: 10.1242/jcs.50.1.345. View

Moon R, Sharaf H, Hastings C, Ho Y, Nair M, Rchiad Z . Normocyte-binding protein required for human erythrocyte invasion by the zoonotic malaria parasite Plasmodium knowlesi. Proc Natl Acad Sci U S A. 2016; 113(26):7231-6. PMC: 4933575. DOI: 10.1073/pnas.1522469113. View

10.

Asada M, Goto Y, Yahata K, Yokoyama N, Kawai S, Inoue N . Gliding motility of Babesia bovis merozoites visualized by time-lapse video microscopy. PLoS One. 2012; 7(4):e35227. PMC: 3323635. DOI: 10.1371/journal.pone.0035227. View

11.

Knuepfer E, Wright K, Prajapati S, Rawlinson T, Mohring F, Koch M . Divergent roles for the RH5 complex components, CyRPA and RIPR in human-infective malaria parasites. PLoS Pathog. 2019; 15(6):e1007809. PMC: 6588255. DOI: 10.1371/journal.ppat.1007809. View

12.

Kudryashev M, Munter S, Lemgruber L, Montagna G, Stahlberg H, Matuschewski K . Structural basis for chirality and directional motility of Plasmodium sporozoites. Cell Microbiol. 2012; 14(11):1757-68. PMC: 4116596. DOI: 10.1111/j.1462-5822.2012.01836.x. View

13.

Perrin A, Collins C, Russell M, Collinson L, Baker D, Blackman M . The Actinomyosin Motor Drives Malaria Parasite Red Blood Cell Invasion but Not Egress. mBio. 2018; 9(4). PMC: 6030552. DOI: 10.1128/mBio.00905-18. View

14.

Baum J, Richard D, Healer J, Rug M, Krnajski Z, Gilberger T . A conserved molecular motor drives cell invasion and gliding motility across malaria life cycle stages and other apicomplexan parasites. J Biol Chem. 2005; 281(8):5197-208. DOI: 10.1074/jbc.M509807200. View

15.

Endo T, Tokuda H, Yagita K, Koyama T . Effects of extracellular potassium on acid release and motility initiation in Toxoplasma gondii. J Protozool. 1987; 34(3):291-5. DOI: 10.1111/j.1550-7408.1987.tb03177.x. View

16.

Das S, Lemgruber L, Tay C, Baum J, Meissner M . Multiple essential functions of Plasmodium falciparum actin-1 during malaria blood-stage development. BMC Biol. 2017; 15(1):70. PMC: 5557482. DOI: 10.1186/s12915-017-0406-2. View

17.

Robert-Paganin J, Robblee J, Auguin D, Blake T, Bookwalter C, Krementsova E . Plasmodium myosin A drives parasite invasion by an atypical force generating mechanism. Nat Commun. 2019; 10(1):3286. PMC: 6650474. DOI: 10.1038/s41467-019-11120-0. View

18.

Yahata K, Treeck M, Culleton R, Gilberger T, Kaneko O . Time-lapse imaging of red blood cell invasion by the rodent malaria parasite Plasmodium yoelii. PLoS One. 2012; 7(12):e50780. PMC: 3515438. DOI: 10.1371/journal.pone.0050780. View

19.

Fang H, Gomes A, Klages N, Pino P, Maco B, Walker E . Epistasis studies reveal redundancy among calcium-dependent protein kinases in motility and invasion of malaria parasites. Nat Commun. 2018; 9(1):4248. PMC: 6185908. DOI: 10.1038/s41467-018-06733-w. View

20.

De Niz M, Meibalan E, Mejia P, Ma S, Brancucci N, Agop-Nersesian C . gametocytes display homing and vascular transmigration in the host bone marrow. Sci Adv. 2018; 4(5):eaat3775. PMC: 5966192. DOI: 10.1126/sciadv.aat3775. View