Male-Specific Protein Disulphide Isomerase Function is Essential for Plasmodium Transmission and a Vulnerable Target for Intervention

Autor: Sofia Tapanelli, Katarzyna A. Sala, George K. Christophides, Andrew M. Blagborough, Fiona Angrisano
Přispěvatelé: 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]
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Male
GAMETE FUSION
Plasmodium berghei
Protozoan Proteins
lcsh:Medicine
Isomerase
Pharmacology
0601 Biochemistry and Cell Biology
law.invention
Mice
law
Parasite physiology
631/326/417/1716
HAP2
BERGHEI
lcsh:Science
CANDIDATES
64
631/326/417/2552
Multidisciplinary
SURFACE PROTEIN
article
631/80/470
IMMUNIZATION
3. Good health
Parasite biology
Multidisciplinary Sciences
medicine.anatomical_structure
Transmission (mechanics)
Mechanisms of disease
BLOCKING IMMUNITY
Gamete
Science & Technology - Other Topics
Female
64/60
631/80/304
Antibody
82/1
medicine.drug
inorganic chemicals
Isomerase activity
0299 Other Physical Sciences
030106 microbiology
Protein Disulfide-Isomerases
Bacitracin
Biology
14/1
82/80
03 medical and health sciences
Antimalarials
MALARIA
Malaria Vaccines
medicine
KINASE
Animals
Protein folding
PDI FAMILY
14/35
38/109
Science & Technology
82
lcsh:R
medicine.disease
nervous system diseases
body regions
030104 developmental biology
biology.protein
lcsh:Q
Malaria
Function (biology)
Zdroj: Scientific Reports, Vol 9, Iss 1, Pp 1-14 (2019)
Scientific Reports
ISSN: 2045-2322
DOI: 10.1038/s41598-019-54613-0
Popis: 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.
Databáze: OpenAIRE
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