Schistosoma mansoni: a method for inducing resistance to praziquantel using infected Biomphalaria glabrata snails
Schistosoma mansoni: a method for inducing resistance to praziquantel using infected Biomphalaria glabrata snails
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DOI：
10.1590/s0074-02762011000200006
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发表时间：
2011-03-01
期刊：
影响因子：
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通讯作者：
Mattos, Ana Carolina A
中科院分区：
文献类型：
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作者：
Couto, Flávia FB;Coelho, Paulo Marcos Z;Mattos, Ana Carolina A
为了阐明抗血吸虫耐药性的机制，耐药的曼氏血吸虫实验室分离株是必不可少的。我们开发了一种新的方法来诱导对吡喹酮(PZQ)的抗性，该方法采用连续的药物治疗感染曼氏葡萄球菌的光肩星天牛。用100 mg/kg的PZQ连续处理5天，共3次，每次间隔1周。治疗后，用这些钉螺产生的尾蚴(LE-PZQ)和易感的LE株感染小鼠。感染45天后，分别给予200、400、800 mg/kg的PZQ治疗。治疗30天后，我们观察到，感染LE-PZQ分离株200和400 mg/kg的组小鼠的平均灌流恢复虫数显著高于相同处理的LE株。此外，LE-PZQ株(362 mg/kg)和LE株(68 mg/kg)的ED50(杀灭50%幼虫所需的有效剂量)之间也有显著差异。在体外试验中，LE-PZQ分离物的蠕虫对PZQ的敏感性也较低。因此，利用感染钉螺作为曼氏血吸虫抗药性的实验模型是一种有效、快速、简便和廉价的方法。
To elucidate the mechanisms of antischistosoma resistance, drug-resistant Schistosoma mansoni laboratory isolates are essential. We developed a new method for inducing resistance to praziquantel (PZQ) using successive drug treatments of Biomphalaria glabrata snails infected with S. mansoni. Infected B. glabrata were treated three times with 100 mg/kg PZQ for five consecutive days with a one-week interval between them. After the treatment, the cercariae (LE-PZQ) produced from these snails and the LE strains (susceptible) were used to infect mice. Forty-five days after infection, mice were treated with 200, 400 or 800 mg/kg PZQ. Thirty days post-treatment, we observed that the mean number of worms recovered by perfusion was significantly higher in the group of mice infected with the LE-PZQ isolate treated with 200 and 400 mg/kg in comparison to the LE strain with the same treatment. Moreover, there was a significant difference between the ED50(effective dose required to kill 50% of the worms) of the LE-PZQ isolate (362 mg/kg) and the LE strain (68 mg/kg). In the in vitro assays, the worms of the LE-PZQ isolate were also less susceptible to PZQ. Thus, the use of infected snails as an experimental model for development of resistance to S. mansoni is effective, fast, simple and cheap.