Distinct adaptations of a gametocyte ABC transporter to murine and human Plasmodium parasites and its incompatibility in cross-species complementation
| Autor: | Kai Matuschewski, Taco W. A. Kooij, Melanie C. Ridgway, Manuel Rauch, Simon H. J. Brown, Todd W. Mitchell, Alexander G. Maier, Phuong N. Tran, Sanketha Kenthirapalan |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Plasmodium berghei Plasmodium falciparum 030231 tropical medicine Protozoan Proteins lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] Plasmodium Mice 03 medical and health sciences 0302 clinical medicine parasitic diseases Gametocyte Animals Humans Parasite hosting Malaria Falciparum Gene Genetics biology biology.organism_classification 3. Good health 030104 developmental biology Infectious Diseases Human parasite ATP-Binding Cassette Transporters Female Parasitology Orthologous Gene |
| Zdroj: | International Journal for Parasitology, 50, 511-522 International Journal for Parasitology, 50, 6-7, pp. 511-522 |
| ISSN: | 0020-7519 |
| Popis: | Contains fulltext : 220061.pdf (Publisher’s version ) (Closed access) Parasites of the genus Plasmodium infect a wide range of mammalian hosts including humans, primates, bats and arboreal rodents. A hallmark of Plasmodium spp. is the very narrow host range, indicative of matching parasite-host coevolution. Accordingly, their respective genomes harbour many unique genes and gene families that typically encode proteins involved in host cell recognition and remodelling. Whether and to what extent conserved proteins that are shared across Plasmodium spp. also exert distinct species-specific roles remains largely untested. Here, we present detailed functional profiling of the female gametocyte-specific ATP-binding cassette transporter gABCG2 in the murine parasite Plasmodium berghei and compare our findings with data from the orthologous gene in the human parasite Plasmodium falciparum. We show that P. berghei gABCG2 is female-specific and continues to be expressed in zygotes and ookinetes. In contrast to a distinct localization to Iipid-rich gametocyte-specific spots as observed in P. falciparum, the murine malaria parasite homolog is found at the parasite plasma membrane. Plasmodium berghei lacking gABCG2 displays fast asexual blood-stage replication and increased proportions of female gametocytes, consistent with the corresponding P. falciparum knock-out phenotype. Strikingly, cross-species replacement of gABCG2 in either the murine or the human parasite did not restore normal growth rates. The lack of successful complementation despite high conservation across Plasmodium spp. is an indicator of distinct adaptations and tight parasite-host coevolution. Hence, incompatibility of conserved genes in closely related Plasmodium spp. might be more common than previously anticipated. |
| Databáze: | OpenAIRE |
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