Journal
CELLULAR MICROBIOLOGY
Volume 16, Issue 5, Pages 642-656Publisher
WILEY
DOI: 10.1111/cmi.12287
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Funding
- National Health and Medical Research Council of Australia (NHMRC) [637406]
- Victorian State Government Operational Infrastructure Support grant
- Walter and Eliza Hall Institute of Medical Research
- University of Melbourne (Australia)
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Malaria is caused by obligate intracellular parasites, of which Plasmodium falciparum is the most lethal species. In humans, P.falciparum merozoites (invasive forms of the parasite) employ a host of parasite proteins to rapidly invade erythrocytes. One of these is the P.falciparum apical membrane antigen 1 (PfAMA1) which forms a complex with rhoptry neck proteins at the tight junction. Here, we have placed the Pfama1 gene under conditional control using dimerizable Cre recombinase (DiCre) in P.falciparum. DiCre-mediated excision of the loxP-flanked Pfama1 gene results in approximately 80% decreased expression of the protein within one intraerythrocytic growth cycle. This reduces growth by 40%, due to decreased invasion efficiency characterized by a post-invasion defect in sealing of the parasitophorous vacuole. These results show that PfAMA1 is an essential protein for merozoite invasion in P.falciparum and either directly or indirectly plays a role in resealing of the red blood cell at the posterior end of the invasion event.
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