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bioRxiv · 10.1101/411926

Male-Specific Protein Disulphide Isomerase Function is Essential for Plasmodium Fertilization and Transmission

Angrisano, F.·Sala, K. A.·Tapanelli, S.·Christophides, G. K.·Blagborough, A. M.
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Abstract

Inhibiting transmission of Plasmodium is an essential strategy in malaria eradication, and the biological process of gamete fusion during fertilization is a proven target for this approach. The lack of knowledge of the mechanisms underlying fertilization have been a hindrance in the development of transmission-blocking interventions. Here we describe a protein disulphide isomerase essential for malarial transmission (PDI-Trans/PBANKA_0820300) to the mosquito. We show that PDI-Trans activity is male-specific, surface expressed, essential for fertilization/transmission, and exhibits disulphide isomerase activity which is up-regulated post-gamete activation. We demonstrate that PDI-Trans is a viable anti-malarial drug and vaccine target blocking malarial transmission with the use of the PDI inhibitor bacitracin (98.21%/92.48% reduction in intensity/prevalence), and anti-PDI-Trans peptide antibodies (66.22%/33.16% reduction in intensity/prevalence). To our knowledge, these results provide the first primary evidence that protein disulphide isomerase function is essential for malarial transmission, and emphasize the potential of anti-PDI agents to act as anti-malarials, facilitating the future development of novel transmission-blocking compounds or vaccines.

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Angrisano, F., Sala, K. A., Tapanelli, S., Christophides, G. K., Blagborough, A. M.. 2018-09-09. Male-Specific Protein Disulphide Isomerase Function is Essential for Plasmodium Fertilization and Transmission. https://doi.org/10.1101/411926

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