PT  - JOURNAL ARTICLE
AU  - Fiona Angrisano
AU  - Katarzyna A. Sala
AU  - Sofia Tapanelli
AU  - George K. Christophides
AU  - Andrew M. Blagborough
TI  - Male-Specific Protein Disulphide Isomerase Function is Essential for <em>Plasmodium</em> Fertilization and Transmission
AID  - 10.1101/411926
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 411926
4099  - http://biorxiv.org/content/early/2018/09/09/411926.short
4100  - http://biorxiv.org/content/early/2018/09/09/411926.full
AB  - 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.