Why can’t artemisinin kill babesia like plasmodium can? Parasites and vectors

Babesia is an intra-erythrocyte apicomplex that digests and uses erythrocytes in the same way as intra-erythrocyte plasmodia, but unlike the latter, is insensitive to artemisinin. A comparison of the genomes of Babesia and Plasmodium showed that the Babesia genome is smaller than that of Plasmodium and lacks many genes, especially those related to heme synthesis found in the latter. Single cell sequencing analysis showed that different treatment groups of Babesia microti expressing genes associated with the pentose phosphate pathway, DNA replication, antioxidants, glycolysis, and glutathione were less sensitive to artemether than joe Plasmodium 17XNL. In particular, genes associated with the pentose phosphate pathway, genes associated with DNA replication, and genes associated with glutathione, which were actively expressed in P. yoelii 17XNL, were not actively expressed in voles. The addition of iron to the body can promote the reproduction of Bacillus microti. These results suggest that Babesia spp. The absence of a mechanism for the utilization of heme or iron in hemoglobin, similar to that of Plasmodium, which may contribute to their insensitivity to artemisinin.
The hemolytic disease babesiosis is caused by protozoan parasites of the genus Babesia. More than 100 species of Babesia have been identified, some of which turned out to be pathogenic for humans. More than 100 Plasmodium species have also been identified, five of which cause malaria in humans. Both Babesia and Plasmodium are intraerythrocyte protozoa that are associated with common clinical symptoms such as hemolytic anemia, fever, cholinergia, hemoglobinuria, and splenomegaly . Two hosts participate in the life cycle of these genera: vertebrates and arthropods. When feeding on blood, the latter can deliver sporozoites to the vertebrate host and infect erythrocytes. However, malaria parasites first invade liver cells, then infect red blood cells (erythrocytes), where they reproduce asexually. After these stages, both Babesia and Plasmodium differentiate into male and female gametocytes. They are ingested by the arthropod host, where the gametes combine and go through a cycle of sporogenesis, resulting in the formation of sporozoites. A new cycle begins when an arthropod host bites a new vertebrate host. These two genera of endoprotozoal parasites have similar life cycles, morphology, and pathogenicity, and have similar vertebrate and arthropod vectors, so they are often confused despite their reproductive, export, and parasitic vacuole roles. There are differences.
Interestingly, although artemisinin and its derivatives (ART) are effective in killing malaria parasites, they only marginally inhibit the growth of Babesia species. Although both Babesia and Plasmodium can digest hemoglobin amino acids, only Plasmodium spp. Plasmodium is produced during this metabolic process. Plasmodial pigments were previously thought to be insoluble metabolic by-products of hemoglobin digestion during parasitic infection of red blood cells, with no biological function. However, accumulating evidence suggests that Plasmodium plays a critical role in free heme detoxification and iron storage and utilization. In particular, malaria parasites maintain a high level of hemoglobin (1.6 µmol/L) throughout their development in erythrocytes, much higher than in other parasites [10]. In addition, the accumulation of plasmozoin in Plasmodium gametocytes suggests that plasmozoin is biologically important for the reproduction of species in this genus. Interestingly, Plasmodium parasites that cannot synthesize Plasmodium are morphologically and pathogenetically similar to Babesia and are less virulent and less reproductive than Plasmodium parasites that can synthesize Plasmodium, for example, found in some chloroquine-resistant Plasmodium species. matter.
It is not clear why babesias do not produce plasmochrome (a heme polymer that stores large amounts of HI). Malaria parasites are sensitive to iron chelators, suggesting that they are more dependent on iron than non-susceptible organisms. In particular, recent studies have shown that artemisinin kills Plasmodium via interference effects via HI. It appears that Plasmodium and Babesia have different HI requirements, which may be due to their different sensitivity to ART. How is it different from Plasmodium, Babesia. Whether HI is not required or stored in large quantities and does not produce plasmazoites, it remains to be seen whether the different HI requirements of these species determine their different fecundity. To explore the mechanisms underlying these differences, we compared the genomes of P. yoelii and B. microti, analyzed the effects of artemether on P. yoelii 17XNL and B. microti using single-cell transcriptome sequencing, and examined iron supply.


Post time: Jun-27-2023