Male-Specific Protein Disulphide Isomerase Function is Essential for Plasmodium Transmission and a Vulnerable Target for Intervention
Sala, Katarzyna A.
Blagborough, Andrew M.
Nature Publishing Group UK
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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)https://doi.org/10.1038/s41598-019-54613-0
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. 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.
Article, /631/80/304, /631/80/470, /631/326/417/1716, /631/326/417/2552, /64, /82, /14/1, /14/35, /38/109, /64/60, /82/1, /82/80, article
RCUK | Medical Research Council (MRC) (MR/N00227X/1)
External DOI: https://doi.org/10.1038/s41598-019-54613-0
This record's URL: https://www.repository.cam.ac.uk/handle/1810/314440
Attribution 4.0 International (CC BY 4.0)
Licence URL: https://creativecommons.org/licenses/by/4.0/