Standard Selection Treatments with Sulfadiazine Limit Plasmodium yoelii Host-to-Vector Transmission.
Standard Selection Treatments with Sulfadiazine Limit Plasmodium yoelii Host-to-Vector Transmission.
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一些已失去临床效用的抗疟药物已被重新用于实验性应用。一个例子是磺胺嘧啶，一种对氨基苯甲酸（pABA）的类似物，它抑制寄生虫的叶酸合成途径以阻断DNA合成。磺胺嘧啶治疗感染约氏疟原虫和伯氏疟原虫的小鼠通常用于通过杀死无性血液阶段寄生虫来富集配子体，但尚不清楚是否对传播有下游影响。为了确定磺胺嘧啶暴露对传播是否有显著影响，我们将约氏疟原虫（17 XNL株）寄生虫传播给斯氏按蚊，并评估了不同磺胺嘧啶治疗条件下感染的患病率和强度。我们观察到，如果寄生虫暴露于小鼠宿主或蚊子载体中的磺胺嘧啶，受感染的蚊子数量和感染强度都会减少。如果给蚊子提供新鲜的pABA，磺胺嘧啶治疗可以稍微克服。相比之下，我们确定暴露于磺胺嘧啶的配子母细胞可以在体外发育成形态成熟的动合子，因此如果药物被洗掉并且寄生虫在培养基中补充有pABA，则磺胺嘧啶在宿主中的暴露可能是可逆的。总体而言，这表明磺胺嘧啶抑制宿主-载体传播，并且这种抑制只能通过在体内和体外暴露于新鲜的PABA而部分克服。由于配子体是非常感兴趣的发展传播阻断干预措施，我们建议使用破坏性较小的方法配子体富集。重要性在这项工作中，我们发现了一个实质性的问题，有多少研究的性阶段的啮齿动物疟原虫进行。简单地说，性血液阶段疟原虫寄生虫或配子体的分离对于研究疟疾的传播前和传播阶段生物学至关重要。在啮齿动物感染性疟疾模型中分离这一特定阶段的常规方法是用磺胺嘧啶进行药物治疗，磺胺嘧啶是一种抗叶酸剂，可选择性杀死活跃复制的无性血液阶段寄生虫，但不杀死配子体。因此，研究人员使用这种方法作为一种方便的方法来生产高度富集的配子母细胞样品。然而，在这项工作中，我们描述了磺胺嘧啶的标准药物选择不仅可以杀死无性血液阶段的寄生虫，而且还可以显著影响宿主到媒介的传播。
Some antimalarial drugs that have lost clinical usefulness have been repurposed for experimental applications. One example is sulfadiazine, an analog of p-aminobenzoic acid (pABA), which inhibits the parasite’s folate synthesis pathway to block DNA synthesis. Sulfadiazine treatment of mice infected with Plasmodium yoelii and P. berghei is routinely used to enrich for gametocytes by killing asexual blood-stage parasites, but it is not well known if there are downstream effects on transmission. To determine if there was a significant effect of sulfadiazine exposure upon transmission, we transmitted Plasmodium yoelii (17XNL strain) parasites to Anopheles stephensi mosquitoes and evaluated the prevalence and intensity of infection under different sulfadiazine treatment conditions. We observed that there was a reduction in both the number of mosquitoes that became infected and in the intensity of infection if parasites were exposed to sulfadiazine in the mouse host or mosquito vector. Sulfadiazine treatment could be marginally overcome if mosquitoes were provided fresh pABA. In contrast, we determined that gametocytes exposed to sulfadiazine could develop into morphologically mature ookinetes in vitro, thus sulfadiazine exposure in the host may be reversible if the drug is washed out and the parasites are supplemented with pABA in the culture media. Overall, this indicates that sulfadiazine dampens host-to-vector transmission and that this inhibition can only be partially overcome by exposure to fresh pABA in vivo and in vitro. Because gametocytes are of great interest for developing transmission-blocking interventions, we recommend the use of less disruptive approaches for gametocyte enrichment. IMPORTANCE In this work, we have uncovered a substantial problem with how many studies of the sexual stages of rodent malaria parasites are conducted. Briefly, the isolation of sexual blood-stage Plasmodium parasites, or gametocytes, is essential to study pretransmission and transmission-stage biology of malaria. A routine method for the isolation of this specific stage in rodent-infectious malaria models is drug treatment with sulfadiazine, an antifolate that selectively kills actively replicating asexual blood-stage parasites but not gametocytes. Thus, researchers use this as a convenient way to produce highly enriched gametocyte samples. However, in this work, we describe how this standard drug selection with sulfadiazine not only kills asexual blood-stage parasites but also substantially impacts host-to-vector transmission.
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影响因子：
4.6
作者：
Parra M;Yang J;Weitner M;Akkoyunlu M
通讯作者：
Akkoyunlu M
DOI：
10.1016/0035-9203(71)90014-9
发表时间：
1971-01-01
影响因子：
2.2
作者：
GERBERG, EJ
通讯作者：
GERBERG, EJ
影响因子：
10.5
作者：
Aly AS;Vaughan AM;Kappe SH
通讯作者：
Kappe SH
影响因子：
2.4
作者：
JANSE, CJ;MONS, B;VANDERKAAY, HJ
通讯作者：
VANDERKAAY, HJ
影响因子：
8.8
作者：
Matz, Joachim Michael;Watanabe, Mutsumi;Matuschewski, Kai
通讯作者：
Matuschewski, Kai