Male-specific protein disulphide isomerase function is essential for plasmodium transmission and a vulnerable target for intervention
Nature Publishing Group, 2019
Online
academicJournal
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: | Angrisano, F ; Sala, K ; Tapanelli, S ; Christophides, G ; Blagborough, A ; Medical Research Council (MRC) ; Bill & Melinda Gates Foundation |
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Veröffentlichung: | Nature Publishing Group, 2019 |
Medientyp: | academicJournal |
ISSN: | 2045-2322 (print) |
DOI: | 10.1038/s41598-019-54613-0 |
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