Kazuhide Yahata, a , b , 1 , 2 Melissa N. Hart, c , 1 Heledd Davies, b Masahito Asada, a , d Samuel C. Wassmer, c Thomas J. Templeton, a Moritz Treeck, b Robert W. Moon, c , 2 and Osamu Kaneko a
"aDepartment of Protozoology, Institute of Tropical Medicine (NEKKEN), Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan;
bSignalling in Apicomplexan Parasites Laboratory, The Francis Crick Institute, London NW1 1AT, United Kingdom;
cFaculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London WC1E 7HT, United Kingdom;
dNational Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Nishi 2-11, Obihiro, Hokkaido 080-0834, Japan
2To whom correspondence may be addressed. Email: [email protected] or [email protected]
Edited by L. David Sibley, Washington University in St. Louis, St. Louis, MO, and approved October 15, 2021 (received for review August 17, 2021)
Author contributions: K.Y., M.N.H., M.A., S.C.W., M.T., R.W.M., and O.K. designed research; K.Y., M.N.H., and S.C.W. performed research; H.D., M.A., and S.C.W. contributed new reagents/analytic tools; K.Y., M.N.H., H.D., M.A., S.C.W., T.J.T., M.T., R.W.M., and O.K. analyzed data; and K.Y., M.N.H., T.J.T., M.T., R.W.M., and O.K. wrote the paper.
1K.Y. and M.N.H. contributed equally to this work."
"Plasmodium 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 Plasmodium 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, Plasmodium falciparum and Plasmodium knowlesi, 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.
DOI: https://dx.doi.org/ 10.1073/pnas.2114442118
All parasites were observed by differential interference contrast or bright field at 1.5 V/100 W of halogen lamp or LED light (pT-100; CoolLED) to minimize cell damage.
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The pT-100 is a compact and simple-to-use LED illumination system for transmitted light applications, including brightfield, darkfield, DIC, Dodt gradient contrast and phase contrast.
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