The transcriptome of circulating sexually committed Plasmodium falciparum ring stage parasites forecasts malaria transmission potential.

The transcriptome of circulating sexually committed Plasmodium falciparum ring stage parasites forecasts malaria transmission potential.
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循环性致力的恶性疟原虫寄生虫的转录组预测了疟疾的传播潜力。

DOI:
10.1038/s41467-020-19988-z
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发表时间:
2020-12-02
影响因子:
16.6
通讯作者:
Williamson KC
Williamson KC
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Prajapati SK;Ayanful-Torgby R;Pava Z;Barbeau MC;Acquah FK;Cudjoe E;Kakaney C;Amponsah JA;Obboh E;Ahmed AE;Abuaku BK;McCarthy JS;Amoah LE;Williamson KC

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疟疾通过称为配子体的有性阶段寄生虫传播。然而,对于恶性疟原虫,配子母细胞只有在成熟并可传播给蚊子时才能在外周血中检测到,这使得控制工作复杂化。在这里,我们确定了一组基因过表达的患者血液样本与高水平的配子体承诺的环形阶段寄生虫。所有18个基因的表达受转录因子AP 2-G调节,这是配子体发生所必需的。我们选择了三个基因,不表达在成熟的配子体,开发作为生物标志物。我们使用6种不同的寄生虫系在体外验证了所有三种生物标志物,并开发了一种算法,该算法预测了离体样品和志愿者感染研究中的配子体产生。这些生物标志物也足够敏感,可以监测无症状恶性疟原虫携带者的配子体产生,从而可以早期检测和治疗感染性储库,以及对调节性转换的因素进行体内分析。疟疾配子体是有性阶段的寄生虫,从哺乳动物宿主的血液传播回它们的昆虫载体。在这里,Prajapati等人确定了配子体承诺的环阶段生物标志物,可以预测疟疾传播潜力。
Malaria is spread by the transmission of sexual stage parasites, called gametocytes. However, with Plasmodium falciparum, gametocytes can only be detected in peripheral blood when they are mature and transmissible to a mosquito, which complicates control efforts. Here, we identify the set of genes overexpressed in patient blood samples with high levels of gametocyte-committed ring stage parasites. Expression of all 18 genes is regulated by transcription factor AP2-G, which is required for gametocytogenesis. We select three genes, not expressed in mature gametocytes, to develop as biomarkers. All three biomarkers we validate in vitro using 6 different parasite lines and develop an algorithm that predicts gametocyte production in ex vivo samples and volunteer infection studies. The biomarkers are also sensitive enough to monitor gametocyte production in asymptomatic P. falciparum carriers allowing early detection and treatment of infectious reservoirs, as well as the in vivo analysis of factors that modulate sexual conversion. Malaria gametocytes are sexual-stage parasites transmitted from mammalian host’s blood back to their insect vector. Here, Prajapati et al. identify gametocyte-committed ring-stage biomarkers allowing to forecast malaria transmission potential.
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发表时间: 2014-07-09
影响因子: 17.1
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发表时间: 2017-02-01
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