TRANSMISSION-BLOCKING ACTIVITY OF A CHITINASE INHIBITOR AND ACTIVATION OF MALARIAL PARASITE CHITINASE BY MOSQUITO PROTEASE
TRANSMISSION-BLOCKING ACTIVITY OF A CHITINASE INHIBITOR AND ACTIVATION OF MALARIAL PARASITE CHITINASE BY MOSQUITO PROTEASE
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DOI：
10.1073/pnas.90.9.4266
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发表时间：
1993-05-01
影响因子：
11.1
通讯作者：
KASLOW, DC
中科院分区：
文献类型：
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作者：
SHAHABUDDIN, M;TOYOSHIMA, T;KASLOW, DC
在蚊子中肠发育过程中，疟疾寄生虫必须穿过食物团周围形成的含有几丁质的围食基质（PM）。此前 Huber 等人。 [Huber, M.、Cabib, E. 和 Miller, L. H. (1991) Proc.国家。阿卡德。科学。 USA 88, 2807-2810]报道了寄生虫分泌一种具有几丁质酶活性的蛋白质，他们认为寄生虫几丁质酶（EC 3.2.1.14）在寄生虫从血粉中排出的过程中起着重要作用。我们发现异糖酰胺是一种几丁质酶的特异性抑制剂，可以完全阻断体内卵囊的发育，从而阻断疟疾寄生虫的传播。在血粉中添加外源几丁质酶可防止 PM 形成并逆转异糖脒的传输阻断活性。使用外源几丁质酶，我们还发现 PM 不会限制发育成卵囊的寄生虫数量，这表明寄生虫产生足够量的几丁质酶来穿透这一势垒。此外，我们发现用来自蚊子中肠的二异丙基氟磷酸敏感胰蛋白酶样蛋白酶或内切蛋白酶 Lys-C 处理寄生虫几丁质酶可增加其酶活性。这些结果表明疟疾寄生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。
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.