Malaria Pigment Crystals, the Achilles Heel of the Malaria Parasite

Nanocrystallography measurements of early stage synthetic malaria pigment

Journal of Applied Crystallography ◽

10.1107/s1600576717012663 ◽

2017 ◽

Vol 50 (5) ◽

pp. 1533-1540 ◽

Cited By ~ 6

Author(s):

Ruben A. Dilanian ◽

Victor Streltsov ◽

Hannah D. Coughlan ◽

Harry M. Quiney ◽

Andrew V. Martin ◽

...

Keyword(s):

Free Electron Laser ◽

Malaria Parasite ◽

Early Stage ◽

Simulation Studies ◽

X Ray ◽

Additional Information ◽

Structural Differences ◽

Malaria Pigment ◽

Damage Simulation ◽

Crystalline Forms

The recent availability of extremely intense, femtosecond X-ray free-electron laser (XFEL) sources has spurred the development of serial femtosecond nanocrystallography (SFX). Here, SFX is used to analyze nanoscale crystals of β-hematin, the synthetic form of hemozoin which is a waste by-product of the malaria parasite. This analysis reveals significant differences in β-hematin data collected during SFX and synchrotron crystallography experiments. To interpret these differences two possibilities are considered: structural differences between the nanocrystal and larger crystalline forms of β-hematin, and radiation damage. Simulation studies show that structural inhomogeneity appears at present to provide a better fit to the experimental data. If confirmed, these observations will have implications for designing compounds that inhibit hemozoin formation and suggest that, for some systems at least, additional information may be gained by comparing structures obtained from nanocrystals and macroscopic crystals of the same molecule.

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Description, measurement, and automatic classification of the Plasmodium berghei oocyst morphology during early differentiation

10.1101/2020.09.15.299024 ◽

2020 ◽

Author(s):

Benito Recio-Tótoro ◽

Adán Guerrero ◽

Humberto Lanz-Mendoza

Keyword(s):

Plasmodium Berghei ◽

Malaria Parasite ◽

Computer Training ◽

Training Algorithm ◽

Morphological Transformation ◽

Redox Modulation ◽

Morphometric Measurements ◽

Cell Content ◽

Malaria Pigment

AbstractAfter colonization of the mosquito midgut by the malaria parasite, Plasmodium differentiates from an invasive, motile ookinete to a multiplicative, sessile oocyst. Despite their importance in establishing the infection and increasing its population, the morphological transformation associated with these changes in function has been scarcely explored. Oocyst differentiation begins with the formation of a spherical protrusion near the center of the crescent-shaped ookinete. As this protuberance grows, it engulfs the content of the two distal ends, thus rounding the cell. In this work, scrutinized observations of the overall changes in shape, coupled with the migration of the malaria pigment granules and the nucleus into the protuberance, revealed that the movement of the cell content happens in an anteroposterior manner. The resulting data, formalized as morphometric measurements, led to the identification of 5 transitional stages and to the development of a computer training algorithm that automatically classifies them. Since cell differentiation has been associated with redox fluctuations, the classification algorithm was tested with parasites stained with a glutathione-specific fluorescent probe, revealing a redox modulation during differentiation.

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