A snake venom phospholipase A(2) blocks malaria parasite development in the mosquito midgut by inhibiting ookinete association with the midgut surface.
A snake venom phospholipase A(2) blocks malaria parasite development in the mosquito midgut by inhibiting ookinete association with the midgut surface.
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发表时间：
2001-12
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通讯作者：
H. Zieler;David B. Keister;James A. Dvorak;José M. C. Ribeiro
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作者：
H. Zieler;David B. Keister;James A. Dvorak;José M. C. Ribeiro
卵囊的形成是蚊子体内疟原虫发育的关键阶段。我们发现，当将东方小菜斑响尾蛇（Crotalus adamanteus）毒液中的磷脂酶 A(2) (PLA2) 添加到受感染的鸡血中并喂给蚊子时，会抑制卵囊的形成。其他蛇和蜜蜂的毒液中的 PLA2 也具有类似的传播阻断活性。这种效应在禽类疟疾寄生虫鸡疟原虫和人类寄生虫恶性疟原虫在各自的蚊子宿主中发育时都可以看到。即使在 PLA2 活性位点的不可逆抑制剂存在的情况下，也会发生抑制作用，表明抗寄生虫作用不需要酶的水解活性。当将酶与动动子一起喂给蚊子时，也会出现抑制作用，这表明抑制发生在动动子成熟后。 PLA2 对寄生虫没有直接作用。然而，用 PLA2（催化活性或非活性）预处理中肠会显着降低体外动合蛋白/中肠关联的水平。因此，PLA2 似乎是通过与中肠表面结合并防止动动分子附着到该表面来发挥作用的。因此，PLA2 是在转基因蚊子中表达作为抑制疟疾传播的一种极好的候选者。
Oocyst formation is a critical stage in the development of the malaria parasite in the mosquito. We have discovered that the phospholipase A(2) (PLA2) from the venom of the eastern diamondback rattlesnake (Crotalus adamanteus) inhibits oocyst formation when added to infected chicken blood and fed to mosquitoes. A similar transmission-blocking activity was demonstrated for PLA2s from the venom of other snakes and from the honeybee. This effect is seen both with the avian malaria parasite Plasmodium gallinaceum and with the human parasite Plasmodium falciparum developing in their respective mosquito hosts. The inhibition occurs even in the presence of an irreversible inhibitor of the active site of PLA2, indicating that the hydrolytic activity of the enzyme is not required for the antiparasitic effect. Inhibition is also seen when the enzyme is fed to mosquitoes together with ookinetes, suggesting that the inhibition occurs after ookinete maturation. PLA2 has no direct effect on the parasite. However, pretreatment of midguts with PLA2 (catalytically active or inactive) dramatically lowers the level of ookinete/midgut association in vitro. It appears, therefore, that PLA2 is acting by associating with the midgut surface and preventing ookinete attachment to this surface. Thus, PLA2 is an excellent candidate for expression in transgenic mosquitoes as a means of inhibiting the transmission of malaria.