Malaria parasites remodel their host erythrocytes to gain nutrients and avoid the immune system. Host erythrocytes are modified by hundreds of effector proteins exported from the parasite into the host cell. Protein export is mediated by the PTEX translocon comprising five core components of which EXP2 is considered to form the putative pore that spans the vacuole membrane enveloping the parasite within its erythrocyte. To explore the function and importance of EXP2 for parasite survival in the asexual blood stage of Plasmodium falciparum we inducibly knocked down the expression of EXP2. Reduction in EXP2 expression strongly reduced parasite growth proportional to the degree of protein knockdown and tended to stall development about half way through the asexual cell cycle. Once the knockdown inducer was removed and EXP2 expression restored, parasite growth recovered dependent upon the length and degree of knockdown. To establish EXP2 function and hence the basis for growth reduction, the trafficking of an exported protein was monitored following EXP2 knockdown. This resulted in severe attenuation of protein export and is consistent with EXP2, and PTEX in general, being the conduit for export of proteins into the host compartment.
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We thank the Australian Red Cross Blood Bank for the provision of human blood, Jacobus
Pharmaceuticals for providing WR99210 and Monash Micro Imaging. We are grateful to
Leann Tilley and Brian Cooke for providing ERC and SBP1 antibodies and Eva Pesce and
Thorey Jonsdottir for technical assistance. The authors gratefully acknowledge funding from
the Victorian Operational Infrastructure Support Program received by the Burnet Institute
and for grants from the National Health and Medical Research Council of Australia (1068287,
1128198 and 1092789).