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Endogenously-expressed NH2-terminus of circumsporozoite protein interferes with sporozoite invasion of mosquito salivary glands
Registro en:
KOJIN, Bianca B. et al. Endogenously-expressed NH2-terminus of circumsporozoite protein interferes with sporozoite invasion of mosquito salivary glands. Malaria Journal, v.15:153, 11p, 2016.
1475-2875
10.1186/s12936-016-1207-8
1475-2875
Autor
Kojin, Bianca B.
Silva, André Luis Costa da
Maciel, Ceres
Henriques, Dayane Alves
Carvalho, Danilo O.
Martin, Kelcie
Marinotti, Osvaldo
James, Anthony A.
Bonaldo, Myrna C.
Capurro, Margareth Lara
Resumen
Background: The circumsporozoite protein is the most abundant polypeptide expressed by sporozoites, the malaria
parasite stage capable of infecting humans. Sporozoite invasion of mosquito salivary glands prior to transmission
is likely mediated by a receptor/ligand-like interaction of the parasites with the target tissues, and the amino (NH2)terminal
portion of CSP is involved in this interaction but not the TSR region on the carboxyl (C)-terminus. Peptides
based on the NH2-terminal domain could compete with the parasites for the salivary gland receptors and thus inhibit
penetration.
Methods: Peptides based on the NH2-terminus and TSR domains of the CSP from avian or human malaria para‑
sites, Plasmodium gallinaceum and Plasmodium falciparum, respectively, were expressed endogenously in mosquito
haemolymph using a transient (Sindbis virus-mediated) or stable (piggyBac-mediated transgenesis) system.
Results: Transient endogenous expression of partial NH2-terminus peptide from P. falciparum CSP in P. gallinaceum-infected
Aedes aegypti resulted in a reduced number of sporozoites in the salivary glands. When a transgenic
approach was used to express a partial CSP NH2-terminal domain from P. gallinaceum the number of sporozoites in
the salivary glands did not show a difference when compared to controls. However, a significant difference could be
observed when mosquitoes with a lower infection were analysed. The same result could not be observed with mos‑
quitoes endogenously expressing peptides based on the TSR domain from either P. gallinaceum or P. falciparum.
Conclusion: These results support the conclusion that CSP partial NH2-terminal domain can be endogenously
expressed to promote a competition for the receptor used by sporozoites to invade salivary glands, and they could
be used to block this interaction and reduce parasite transmission. The same effect cannot be obtained with peptides
based on the TSR domain.