2023 Author: Bryan Walter | [email protected]. Last modified: 2023-05-21 22:24
Development cycle of Plasmodium falciparum in erythrocytes
American biologists have proved that the cyclical course of malaria is due to the presence of its own circadian rhythms in the malaria plasmodium, which can be observed even in culture in vitro and during infection of an "asynchronous" host. The results of the experiments are presented at once in two articles in Science (1, 2).
Malaria is a serious infectious disease caused by the protozoan of the genus Plasmodium. The pathogen enters the blood of the victim with the bite of a certain type of mosquito, and begins to multiply inside first liver cells, and then in erythrocytes - red blood cells. Malaria is characterized by recurrent fever that occurs every 24, 48, or 72 hours. The cyclical nature of the disease corresponds to the cyclical development of plasmodia, which simultaneously destroy erythrocytes and come out.
Previously, it was believed that the developmental cycles of the parasite are regulated by the circadian rhythms of the host, but scientists have found that plasmodia are mainly guided by their own biological clock, which, nevertheless, can adjust to the clock of their host. Two different research groups on two species of Plasmodium monitored the expression of parasite genes and were convinced of its cyclicity, regardless of external conditions.
Scientists at the University of Texas Southwestern Medical Center worked on a mouse model of malaria, which is caused by the protozoan Pla smodium chabaudi, and studied the parasite's transcriptome every 3 hours for three 24-hour cycles. They found that the expression of 60 percent of plasmodium genes is subject to regular fluctuations within the 24-hour cycle, which persisted in the down-mode mice. In the first case, the infected mice were kept in the dark, disrupting their sleep regimen, and in the second case, they were fed randomly during the day, breaking the diet. It turned out that neither one nor the other affects the development cycle of the plasmodium.
Plasmodium cyclicity was observed even in mutant mice with the Cry gene turned off, which did not have any daily routine from birth. Nevertheless, after 5-7 days of infection, the synchronicity of the parasite cycles in these mice disappeared. In mutant mice with days extended to 26 hours (i.e., their daily activity was within 25.7 hours, while in normal mice at 23.7 hours), the life cycle of the plasmodium stretched out according to the master's. The researchers concluded that each malaria plasmodium regulates its life cycle on its own, but is also able to perceive signals from the host's body, which, apparently, help to synchronize the parasite population.
A research team from Duke University studied the behavior of four strains of human malaria, P. lasmodium falciparum, in culture in vitro. Scientists also analyzed the RNA composition of plasmodia at intervals of 3 hours for 60-70 hours. They found that at least 87 percent of Plasmodium transcripts are subject to cyclic fluctuations. It should be noted that plasmodia do not have genes homologous to the main circadian regulators of animals; nevertheless, even in culture, their life cycle was 48 hours with slight variations from strain to strain.
Scientists' observations are consistent with the existing theory that in the composition of the body, each cell has its own biological clock (circadian rhythms), but their cycle is not necessarily exactly 24 hours. To adjust all cellular clocks, a “master regulator” is needed, which in mammals is located in the hypothalamus. For the discovery of the biological clock and the mechanism of work in 2017, the Nobel Prize in Physiology or Medicine was awarded, you can read more about this in our material "The clock is only one-sounding."
