Male-Specific Protein Disulphide Isomerase Function is Essential for Plasmodium Transmission and a Vulnerable Target for Intervention.
Sala, Katarzyna A
Blagborough, Andrew Michael
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Angrisano, F., Sala, K. A., Tapanelli, S., Christophides, G. K., & Blagborough, A. M. (2019). Male-Specific Protein Disulphide Isomerase Function is Essential for Plasmodium Transmission and a Vulnerable Target for Intervention.. Scientific reports, 9 (1), 18300. https://doi.org/10.1038/s41598-019-54613-0
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. 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 PDI inhibitor bacitracin (98.21%/92.48% reduction in intensity/prevalence), and anti-PDI-Trans antibodies (66.22%/33.16% reduction in intensity/prevalence). To our knowledge, these results provide the first evidence that PDI 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 interventions.
Animals, Mice, Plasmodium berghei, Malaria, Bacitracin, Protozoan Proteins, Malaria Vaccines, Antimalarials, Female, Male, Protein Disulfide-Isomerases
This work was funded by the MRC (New Investigator Research Grant; award number MR/N00227X/1).
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External DOI: https://doi.org/10.1038/s41598-019-54613-0
This record's URL: https://www.repository.cam.ac.uk/handle/1810/298976
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