A Novel Ex Vivo Drug Assay for Assessing the Transmission-Blocking Activity of Compounds on Field-Isolated Plasmodium falciparum Gametocytes.
A Novel Ex Vivo Drug Assay for Assessing the Transmission-Blocking Activity of Compounds on Field-Isolated Plasmodium falciparum Gametocytes.
复制标题
DOI：
10.1128/aac.01001-22
复制
发表时间：
2022-12-20
影响因子：
4.9
通讯作者：
Djimde, Abdoulaye A.
中科院分区：
文献类型：
--
作者：
Ouologuem, Dinkorma T.;Dembele, Laurent;Dara, Antoine;Kone, Aminatou K.;Diallo, Nouhoum;Sangare, Cheick P. O.;Ballo, Fatoumata, I;Dao, Francois;Goita, Siaka;Haidara, Aboubecrin S.;Traore, Aliou;Niangaly, Amadou B.;Dama, Souleymane;Sissoko, Sekou;Sogore, Fanta;Dara, Jacob N.;Barre, Yacouba N.;Daou, Amadou;Cisse, Fatoumata;Diakite, Ousmaila;Doumbia, Diagassan;Koumare, Sekou;Fofana, Bakary;Tandina, Fatalmoudou;Sylla, Daman;Sacko, Adama;Coulibaly, Mamadou;Tekete, Mamadou M.;Ouattara, Amed;Djimde, Abdoulaye A.
关键词：
传播阻断疗法的发现和发展对消灭疟疾提出了挑战，需要标准和可重复的生物测定来测量抗疟药物和候选化合物的阻断特性。目前大多数评价化合物的传播阻断活性的生物测定依赖于实验室适应的疟原虫菌株。来自临床配子体分离株的传播阻断数据可以帮助选择新的传播阻断候选药物进行进一步开发。使用新鲜收集的恶性疟原虫配子体从无症状的个人，我们首先优化离体培养条件，以提高配子体的活力和感染性，通过测试几个培养参数。接下来，我们将离体场分离的配子母细胞预暴露于氯喹、双氢青蒿素、伯氨喹、KDU 691、GNF179和安磺灵48小时，然后直接膜喂养。我们测量了药物暴露后药物对按蚊配子体恢复性生活周期能力的活性。使用57个血液样本从马里志愿者年龄在6至15岁，我们证明，新鲜收集的外地配子体的感染性可以保存和改进离体在培养基中补充10%的马血清在4%的红细胞压积为48小时。此外，我们优化的药物分析显示氯喹和双氢青蒿素的传递阻断活性较弱，而伯氨喹和安磺灵在1 μM时表现出约50%的传递阻断活性。KDU 691和GNF179分别在1 μM和5 nM时阻断疟原虫传播。这种新方法，如果实施，有可能加速筛选具有传播阻断活性的化合物。
The discovery and development of transmission-blocking therapies challenge malaria elimination and necessitate standard and reproducible bioassays to measure the blocking properties of antimalarial drugs and candidate compounds. Most of the current bioassays evaluating the transmission-blocking activity of compounds rely on laboratory-adapted Plasmodium strains. Transmission-blocking data from clinical gametocyte isolates could help select novel transmission-blocking candidates for further development. Using freshly collected Plasmodium falciparum gametocytes from asymptomatic individuals, we first optimized ex vivo culture conditions to improve gametocyte viability and infectiousness by testing several culture parameters. We next pre-exposed ex vivo field-isolated gametocytes to chloroquine, dihydroartemisinin, primaquine, KDU691, GNF179, and oryzalin for 48 h prior to direct membrane feeding. We measured the activity of the drug on the ability of gametocytes to resume the sexual life cycle in Anopheles after drug exposure. Using 57 blood samples collected from Malian volunteers aged 6 to 15 years, we demonstrate that the infectivity of freshly collected field gametocytes can be preserved and improved ex vivo in a culture medium supplemented with 10% horse serum at 4% hematocrit for 48 h. Moreover, our optimized drug assay displays the weak transmission-blocking activity of chloroquine and dihydroartemisinin, while primaquine and oryzalin exhibited a transmission-blocking activity of ~50% at 1 μM. KDU691 and GNF179 both interrupted Plasmodium transmission at 1 μM and 5 nM, respectively. This new approach, if implemented, has the potential to accelerate the screening of compounds with transmission-blocking activity.
登录
查看更多内容
影响因子：
3.3
作者：
Coulibaly, Mamadou B.;Gabriel, Erin E.;Duffy, Patrick E.
通讯作者：
Duffy, Patrick E.
影响因子：
5.2
作者：
D'Alessandro, Sarah;Silvestrini, Francesco;Taramelli, Donatella
通讯作者：
Taramelli, Donatella
影响因子：
3.1
作者：
Lensen, AHW;BolmervandeVegte, M;Sauerwein, RW
通讯作者：
Sauerwein, RW
影响因子：
4
作者：
Kone, Aminatou;van de Vegte-Bolmer, Marga;Djimde, Abdoulaye A.
通讯作者：
Djimde, Abdoulaye A.
影响因子：
1.2
作者：
Ghanchi, Najia K.;Khan, Mohammad Hassaan;Beg, Mohammad A.
通讯作者：
Beg, Mohammad A.