Male-Specific Protein Disulphide Isomerase Function is Essential for Plasmodium Transmission and a Vulnerable Target for Intervention
In: Scientific Reports, Jg. 9 (2019), Heft 1, S. 1-14
Online
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Zugriff:
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.
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Male-Specific Protein Disulphide Isomerase Function is Essential for Plasmodium Transmission and a Vulnerable Target for Intervention
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Autor/in / Beteiligte Person: | Tapanelli, Sofia ; Sala, Katarzyna A. ; Christophides, George K. ; Blagborough, Andrew M. ; Angrisano, Fiona ; Christophides, George K [0000-0002-3323-1687] ; Apollo - University of Cambridge Repository ; Medical Research Council (MRC) ; Bill & Melinda Gates Foundation ; Christophides, George K. [0000-0002-3323-1687] |
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Zeitschrift: | Scientific Reports, Jg. 9 (2019), Heft 1, S. 1-14 |
Veröffentlichung: | Nature Publishing Group, 2019 |
Medientyp: | unknown |
ISSN: | 2045-2322 (print) |
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