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Transmission-blocking activity of a chitinase inhibitor and activation of malarial parasite chitinase by mosquito protease.

机译：几丁质酶抑制剂的传递阻断活性和蚊虫蛋白酶激活疟疾寄生虫几丁质酶。

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During development in the mosquito midgut, malarial parasites must traverse a chitin-containing peritrophic matrix (PM) that forms around the food bolus. Previously Huber et al. [Huber, M., Cabib, E. & Miller, L. H. (1991) Proc. Natl. Acad. Sci. USA 88, 2807-2810] reported that the parasite secretes a protein with chitinase activity, and they suggested that parasite chitinase (EC 3.2.1.14) plays an important role in the parasite's egress from the blood meal. We found that allosamidin, a specific inhibitor of chitinase, completely blocked oocyst development in vivo and thus blocked malaria parasite transmission. Addition of exogenous chitinase to the blood meal prevented the PM from forming and reversed the transmission-blocking activity of allosamidin. Using exogenous chitinase, we also found that the PM does not limit the number of parasites that develop into oocysts, suggesting that the parasite produces sufficient quantities of chitinase to penetrate this potential barrier. In addition, we found that treatment of parasite chitinase with a diisopropyl fluorophosphate-sensitive trypsinlike protease from the mosquito midgut or endoproteinase Lys-C increased its enzymatic activity. These results suggest that malaria parasite has evolved an intricate mechanism to adapt to the PM and the protease-rich environment of the mosquito midgut.
机译：在蚊子中肠发育过程中，疟疾寄生虫必须横过在食物团附近形成的含几丁质的营养层（PM）。以前，Huber等人。 [Huber，M.，Cabib，E.＆Miller，L.H.（1991）Proc。 Natl。学院科学USA 88，2807-2810]报道了该寄生虫分泌一种具有几丁质酶活性的蛋白质，并且他们认为寄生虫几丁质酶（EC 3.2.1.14）在该寄生虫从血粉中逸出中起着重要作用。我们发现异几丁胺，几丁质酶的特异性抑制剂，完全阻断了卵囊在体内的发育，从而阻断了疟原虫的传播。在血粉中添加外源几丁质酶可防止PM形成，并逆转异源阿密胺的传递阻断活性。使用外源几丁质酶，我们还发现PM不会限制发展为卵囊的寄生虫的数量，这表明该寄生虫会产生足够数量的几丁质酶穿透此潜在屏障。此外，我们发现用来自蚊子中肠的二异丙基氟磷酸盐敏感的胰蛋白酶样蛋白酶或内蛋白酶Lys-C处理寄生虫几丁质酶会增加其酶促活性。这些结果表明，疟原虫已经进化出一种复杂的机制来适应PM和蚊子中肠富含蛋白酶的环境。

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