Why is Babesia not killed by artemisinin like Plasmodium?

• Published in: Parasites & vectors Vol. 16; no. 1; p. 193
• Main Authors: Si, Wenwen, Fang, Chuantao, Liu, Chuang, Yin, Meng, Xu, Wenyue, Li, Yanna, Yan, Xiaoli, Shen, Yujuan, Cao, Jianping, Sun, Jun
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 08.06.2023; BioMed Central; BMC
• Subjects: Artemether; Artemisinin; Arthropods; Babesia; Babesiosis; Bar codes; Blood cells; Cluster analysis; Comparative analysis; Deoxyribonucleic acid; DNA; DNA biosynthesis; DNA replication; Drug resistance in microorganisms; Drug therapy; Erythrocytes; Gene expression; Genes; Genetic aspects; Genomes; Genomics; Glutathione; Glycolysis; Haem; Haem synthesis; Haemoglobin; Hemoglobin; Human diseases; Informatics; Iron; Laboratory animals; Malaria; Metabolism; Morphology; Parasites; Parasitological research; Pentose; Pentose phosphate pathway; Phosphates; Physiological aspects; Plasmodium; Replication; Sequence analysis; Single-cell sequencing; Vector-borne diseases; China; Pentose phosphate pathway; Plasmodium; Single-cell sequencing; Haem synthesis; Artemisinin; Babesia
• ISSN: 1756-3305; 1756-3305
• DOI: 10.1186/s13071-023-05783-4

Babesia spp. are intraerythrocytic apicomplexans that digest and utilize red blood cells in a similar way to intraerythrocytic Plasmodium spp., but unlike the latter, are not sensitive to artemisinin. A comparison of Babesia and Plasmodium genomes revealed that Babesia genomes, which are smaller than those of Plasmodium, lack numerous genes, and especially haem synthesis-related genes, that are found in the latter. Single-cell sequencing analysis showed that the different treatment groups of Babesia microti with expressed pentose phosphate pathway-related, DNA replication-related, antioxidation-related, glycolysis-related, and glutathione-related genes were not as sensitive to artemether as Plasmodium yoelii 17XNL. In particular, pentose phosphate pathway-related, DNA replication-related, and glutathione-related genes, which were actively expressed in P. yoelii 17XNL, were not actively expressed in B. microti. Supplying iron in vivo can promote the reproduction of B. microti. These results suggest that Babesia spp. lack a similar mechanism to that of malaria parasites through which the haem or iron in hemoglobin is utilized, and that this likely leads to their insensitivity to artemisinin.