In Vitro Culture, Drug Sensitivity, and Transcriptome of Plasmodium Vivax Hypnozoites.
In Vitro Culture, Drug Sensitivity, and Transcriptome of Plasmodium Vivax Hypnozoites.
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DOI：
10.1016/j.chom.2018.01.002
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发表时间：
2018-03-14
影响因子：
30.3
通讯作者：
Bhatia SN
中科院分区：
文献类型：
--
作者：
Gural N;Mancio-Silva L;Miller AB;Galstian A;Butty VL;Levine SS;Patrapuvich R;Desai SP;Mikolajczak SA;Kappe SHI;Fleming HE;March S;Sattabongkot J;Bhatia SN
间日疟原虫感染的独特复发性质是消灭疟疾的主要障碍。感染后，潜伏的肝期形成，催眠虫，逗留数周至数月，然后复发，引起复发性血期感染。我们对催眠虫的生物学知之甚少；目前缺乏明确的生物标志物，需要支持表型研究的体外平台。在这里，我们用包含微模式原代人肝细胞共培养（mpcc）的多孔格式在体外概括了间日疟原虫的整个肝脏阶段。mpcc具有间日疟原虫生物学的关键方面，包括建立持久的小形式和生长的分裂体，粒质体释放和随后的网织红细胞感染。我们发现小的形式表现出先前描述的催眠子的特征，我们试点mpcc作为测试候选抗催眠子药物的工具。最后，我们采用混合捕获策略和RNA-seq来描述催眠子石的转录组，并深入了解其生物学。间日疟原虫催眠子由于缺乏人体肝脏平台而难以研究。Gural等人在体外重现了间日疟原虫的整个肝脏阶段，包括催眠子的形成和再激活以及mermersomes的释放。杂化捕获随后的RNAseq揭示了对催眠子岩转录组的第一次观察。
The unique relapsing nature of Plasmodium vivax infection is a major barrier to malaria eradication. Upon infection, dormant liver stage forms, hypnozoites, linger for weeks to months and then relapse to cause recurrent blood stage infection. Very little is known about hypnozoite biology; definitive biomarkers are lacking and in vitro platforms that support phenotypic studies are needed. Here, we recapitulate the entire liver stage of P. vivax in vitro, using a multiwell format that incorporates micropatterned primary human hepatocyte co-cultures (MPCCs). MPCCs feature key aspects of P. vivax biology, including establishment of persistent small forms and growing schizonts, merosome release, and subsequent infection of reticulocytes. We find that the small forms exhibit previously described hallmarks of hypnozoites, and we pilot MPCCs as a tool for testing candidate anti-hypnozoite drugs. Finally, we employ a hybrid capture strategy and RNA-seq to describe the hypnozoite transcriptome and gain insight into its biology. Plasmodium vivax hypnozoites are difficult to study due to lack of human liver platforms. Gural et al. recapitulated the entire liver stage of P. vivax in vitro, including formation and reactivation of hypnozoites and release of merosomes. Hybrid capture followed by RNAseq revealed a first look into the hypnozoite transcriptome.
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激光捕获显微解剖可以实现疟原虫复发物种的分裂和静止肝阶段的转录组分析。
影响因子：
3.4
作者：
Cubi R;Vembar SS;Biton A;Franetich JF;Bordessoulles M;Sossau D;Zanghi G;Bosson-Vanga H;Benard M;Moreno A;Dereuddre-Bosquet N;Le Grand R;Scherf A;Mazier D
通讯作者：
Mazier D
影响因子：
12.3
作者：
Carpenter AE;Jones TR;Lamprecht MR;Clarke C;Kang IH;Friman O;Guertin DA;Chang JH;Lindquist RA;Moffat J;Golland P;Sabatini DM
通讯作者：
Sabatini DM
影响因子：
3.7
作者：
Iwanaga S;Kaneko I;Kato T;Yuda M
通讯作者：
Yuda M
影响因子：
14.9
作者：
Balaji S;Babu MM;Iyer LM;Aravind L
通讯作者：
Aravind L
影响因子：
--
作者：
Auburn, Sarah;Bohme, Ulrike;Otto, Thomas D
通讯作者：
Otto, Thomas D